Written Report on Esophageal Cancer.docx

7/29/2019 Written Report on Esophageal Cancer.docx

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OVERVIEWTo understand esophagus cancer, it helps to know about the normal structure and function of the esophagus first.

ESOPHAGUS

The esophagus is a hollow, muscular tube that connects the throat to the stomach. It lies behind thetrachea (windpipe) and in front of the spine. The wall of the esophagus is made up of several layers of tissue,

including mucous membrane, muscle, and connective tissue

Food and liquids that are swallowed travel through the inside of the esophagus (called the lumen) to

reach the stomach. In adults, the esophagus is usually between 10 and 13 inches long and is about of an inch

across at its smallest point.

The wall of the esophagus has several layers. These layers are important for understanding where cancers in the

esophagus tend to start and how they may grow.

Mucosa: This is the layer that lines the inside of the esophagus. The mucosa has 3 parts: The epitheliumforms the innermost lining of the esophagus and is normally made up of flat, thin cells

called squamous cells. This is where most cancers of the esophagus start.

The lamina propria is a thin layer of connective tissue right under the epithelium. The muscularis mucosais a very thin layer of muscle under the lamina propria.

Submucosa: This is a layer of connective tissue just below the mucosa that contains blood vessels and nerves. Insome parts of the esophagus, this layer also contains glands that secrete mucus.

Muscularis propria: This is a thick band of muscle under the submucosa. This layer of muscle contracts in acoordinated, rhythmic way to push food along the esophagus from the throat to the stomach.

Adventitia: This is the outermost layer of the esophagus, which is formed by connective tissue

Figure 1. Esophagus


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PARTS OF THE ESOPHAGUS

The upper part of the esophagus has a special area of muscle at its beginning that relaxes to open the

esophagus when it senses food or liquid coming toward it. This muscle is called the upper esophageal sphincter.

The lower part of the esophagus that connects to the stomach is called the gastroesophageal (GE)

junction. A special area of muscle near the GE junction, called the lower esophageal sphincter, controls the

movement of food from the esophagus into the stomach and it keeps the stomach's acid and digestive enzymes

out of the esophagus.

Figure 2. Different layers of the walls of the esophagus

Figure 3. Parts of the esophagus


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ESOPHAGEAL CANCEREsophageal cancer can also be referred to as the Cancer of the esophagus.The esophagus is a muscular

tube that extends from the neck to the abdomen and connects the mouth to the stomach. Cancer, or a malignant tumor, is the

result of uncontrolled growth of cells located in a particular region of the body. Cancers can be made of many different types of

cells. Therefore, esophageal cancer occurs when cancer cells develop in the esophagus. The cancer starts at the

inner layer of the esophagus and can spread throughout the other layers of the esophagus and to other parts ofthe body (metastasis).

TWO MAIN TYPES OF ESOPHAGEAL CANCER

1. Squamous cell carcinomaSquamous cells line the inner esophagus, and cancer developing from squamous cells can occur

along the entire esophagus, which, if they degenerate into a malignant tumor, give rise to a type of cancer called

squamous cell cancer. At one time, squamous cell carcinoma was by far the more common type of

esophageal cancer in the United States. This has changed over time, and now it makes up less than half of

esophageal cancers in this country.

2. AdenocarcinomaIt is not normally part of the lining of the esophagus. The very bottom portion of the esophagus and the

region where the esophagus and stomach join are lined with columnar cells that can give rise to malignant tumors

called adenocarcinomas. Before an adenocarcinoma can develop, gland cells must replace an area of

squamous cells, which is what happens in Barrett's esophagus. This occurs mainly in the lower esophagus,

which is the site of most adenocarcinomas.

Figure 4. Images for the esophageal cancer

Figure 5. Images for Squamous cell carcinoma


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Barrett's esophagus

The stomach has strong acid and enzymes that digest food. The epithelium (inner lining) of the

stomach is made of gland cells that release acid, enzymes, and mucus. These cells have special features

that protect them from the stomach's acid and digestive enzymes.

In some people, acid escapes from the stomach back into the esophagus. The medical term for

this isgastroesophageal reflux disease (GERD), or just reflux. In many cases, reflux can cause symptoms

such as heartburn or a burning feeling spreading out from the middle of the chest. But sometimes, reflux

can occur without any symptoms at all.

If reflux of stomach acid into the lower esophagus continues for a long time, it can damage the

lining of the esophagus. This causes the squamous cells that usually line the esophagus to be replaced

with gland cells. These gland cells usually look like the cells that line the stomach and the small intestine

and are more resistant to stomach acid. The presence of gland cells in the esophagus is known as Barrett's

(or Barrett) esophagus.

People with Barrett's esophagus are much more likely to develop cancer of the esophagus. These

people require close medical follow-up in order to find cancer early. Still, although they have a higher risk,

most people with Barrett's esophagus do not go on to develop cancer of the esophagus.

Figure 6. Image for Adenocarcinoma

Figure 7. Barretts esophagus


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OTHER RARE FORMS OF ESOPHAGEAL CANCER

1. SarcomaIt is a rare cancer that arises from transformed cells in one of a number of tissues that develop

from embryonic mesoderm This is in contrast to carcinomas, which originate from epithelial cells. It is

only 0.1-1.5% of all esophageal tumors.

2. Small cell cancer (SCC)It is a rare and highly aggressive tumor associated with a poor prognosis. Histologically, SCC is

characterized by neuroendocrine-like architectural patterns, including nested and trabecular growth with

common features including peripheral palisading and rosette formation in the tumors. It is 0.05 4% of all

esophageal malignancies.

Figure 8. Image for Sarcoma

Figure 9. Image for Small cell cancer (SCC)


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HISTORY OF ESOPHAGEAL CANCERThe history of esophageal cancer dates back to ancient Egyptian times, circa 3000 BC. Since then, the

progress in the diagnosis and treatment of esophageal cancer has been steady. Over the last few centuries there

have been advancements in the visualization and removal of these lesions, but with no real overall impact on

survival rates. The twenty-first century is the time to make major progress in not only improving survival rates, but

also in diagnosing esophageal cancer in the very early stages.

3000 BC-1500 BCSigns of cancer are found on the bones of mummies from ancient Egypt and Peru dating back as far as

3000 BC.

The Edwin Smith Papyrus, which is the oldest written description of cancer known to exist, describes eight

cases of breast tumors or ulcers in Egypt that were treated with cauterization. However, the document also states

that there is no treatmentfor cancer. The original document, written in 3000 BC, was acquired in 1862 by Edwin

Smith at Luxor, Egypt.

1900 BC-1600 BCThe oldest specimen of a human cancer was found in the remains of a female skull dating back to the

Bronze Age. The mummified skeletal remains of Peruvian Incas, dating back 2400 years ago, contained lesions

suggestive of malignant melanoma. And cancer was found in fossilized bones and manuscripts of ancient Egypt.

Cancer is not a disease of our modern industrialized age, as some may have believed at one time.

400 BCHippocrates, known today as the father of medicine, proposed the Humoral Theory of Medicine, which

states that the body is composed of four fluids, or humors: blood, phlegm, yellow bile, and black bile. Any

imbalance of these fluids was thought to cause disease. He attributed cancer to an excess of black bile.

Hippocrates was the first to use the words "carcinos" and "carcinoma" to describe tumors, and hence the term

"cancer" was coined. "Cancer" is derived from the Greek word "karkinos," or crab, which is thought to reference

the appearance of blood vessels on tumors resembling a crab's claws reaching out. He believed that it was best to

leave cancer alone because those who got treatment didn't survive as long.

980 AD-1037 ADAvicenna of Iran is said to have been the first physician to refer to this disease as "cancer of the

esophagus" ("Saratan Be- Mery" in Farsi).

1042 AD-1136 A.DWhat is astounding is that Avicenna, according to the discourses of his second generation pupil, Jorjani

also described the symptoms of cancer of the esophagus. He lived in northeast Iran near the shores of the Caspian

Sea, and was well versed in the teachings of his illustrious predecessor.

More than 2000 years agoMoving to China, researchers encountered a number of references in ancient Chinese medical literature

to this disease. There, cancer of the esophagus was known as "Ye Ge". It is stated in the text of Yi-Guan as

"commonly seen in the elderly and rarely developing in young people".


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1872Theodore Billroth, a German surgeon, performed the first pyloric resection (surgical removal of all or part

of the stomach) for carcinoma. He also was the first (in 1872) to perform an esophageal resection for carcinoma

CONTROVERSY ABOUT THE HISTORY OF ESOPHAGEAL CANCER

There are still many questions about the history of esophageal cancer that need to be answered andsupported by valid evidences since there are still far no proven precursor or causative factor or factors have been

found so it is still a BIG QUESTION MARK for all of us especially for the researchers.

QUESTIONS

1. Is the condition referred to by ancient Chinese and Iranian physicians who had no access to modern medicaltechnology was the same to what is diagnosed today as cancer of the esophagus on the basis of radiologic,

endoscopic and histologic findings?

The first step in such deductive reasoning is to wonder whether the condition referred to by ancientChinese and Iranian physicians and what is diagnosed today as cancer of the esophagus is the same.

2. Can we take the accurate description of esophageal cancer by ancient Chinese and Iranian physicians tomean a higher incidence of the disease in those areas in ancient days?

The next step in knowing the history of a disease is to undergo an inductive process. According to theresearchers, Esophageal cancer is very common in the South-Central Asia, an area that stretches from

the Caucasian mountains across northern Iran, Afghanistan, Kazakhestan, Uzbekistan and

Turkamanistan, into northern China.Keeping in mind that epidemiology is a very modern science, how

does one know that esophageal cancer was common one or two thousand years ago in the "Esophageal

Cancer Belt of South-Central Asia" area"? More common, that is, in comparison to other cancers?

The final question, however, is one that cannot be answered at this time without extensive research:

how can one use historical evidence for the existence of an "Esophageal Cancer Belt of South-Central Asia" to

support either environmental or hereditary risk factors in the etiology of this disease?

Knowing something about the history of medicine might help but will not necessarily solve the riddle of

esophageal cancer, something which must have been a mystery even to our brilliant medical forefathers.

EPIDEMIOLOGYIt is estimated that 17,990 men and women (14,440 men and 3,550 women) will be diagnosed with and

15,210 men and women will die of cancer of the esophagus in 2013. The following information is based on NCIs

SEER Cancer Statistics Review.

INCIDENCE & MORTALITY

SEER Incidence

From 2006-2010, the median age at diagnosis for cancer of the esophagus was 67 years of age.

Approximately 0.0% were diagnosed under age 20; 0.3% between 20 and 34; 2.1% between 35 and 44; 11.9%


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between 45 and 54; 26.9% between 55 and 64; 27.5% between 65 and 74; 23.0% between 75 and 84; and 8.3%

85+ years of age.

The age-adjusted incidence rate was 4.4 per 100,000 men and women per year. These rates are based on

cases diagnosed in 2006-2010 from 18 SEER geographic areas.

Incidence Rates by Race

Race/Ethnicity Male Female

All Races 7.7 per 100,000 men 1.8 per 100,000 women

White 8.0 per 100,000 men 1.8 per 100,000 women

Black 8.4 per 100,000 men 2.7 per 100,000 women

Asian/Pacific Islander 3.9 per 100,000 men 1.1 per 100,000 women

American Indian/Alaska Native 6.1 per 100,000 men 2.4 per 100,000 women

Hispanic 5.2 per 100,000 men 1.0 per 100,000 women

US Mortality

From 2006-2010, the median age at death for cancer of the esophagus was 69 years of age.

Approximately 0.0% died under age 20; 0.2% between 20 and 34; 1.7% between 35 and 44; 10.6% between 45 and

54; 24.7% between 55 and 64; 27.4% between 65 and 74; 24.9% between 75 and 84; and 10.4% 85+ years of age.

The age-adjusted death rate was 4.3 per 100,000 men and women per year. These rates are based on

patients who died in 2006-2010 in the US.

Death Rates by Race

Race/Ethnicity Male Female

All Races 7.6 per 100,000 men 1.6 per 100,000 women

White 7.8 per 100,000 men 1.6 per 100,000 women

Black 7.7 per 100,000 men 2.1 per 100,000 women

Asian/Pacific Islander 3.1 per 100,000 men 0.8 per 100,000 women

American Indian/Alaska Native 6.1 per 100,000 men 1.6 per 100,000 women

Hispanic 4.3 per 100,000 men 0.8 per 100,000 women


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Trends in Rates

Trends in rates can be described in many ways. Information for trends over a fixed period of time, for

example 1996-2010, can be evaluated by the annual percentage change (APC). If there is a negative sign before the

number, the trend is a decrease; otherwise it is an increase. If there is an asterisk after the APC then the trend was

significant, that is, one believes that it is beyond chance, i.e. 95% sure, that the increase or decrease is real over

the period 1996-2010. If the trend is not significant, the trend is usually reported as stable or level. Joinpointanalyses can be used over a long period of time to evaluate when changes in the trend have occurred along with

the APC which shows how much the trend has changed between each of the joinpoints.

The joinpoint trend in SEER cancer incidence with associated APC(%) for cancer of the esophagus between 1975-

2010, All Races

Male and Female Male Female

Trend Period Trend Period Trend Period

0.6* 1975-2004 0.8* 1975-2004 -0.4* 1975-2010

-1.6* 2004-2010 -1.6 2004-2010

The joinpoint trend in US cancer mortality with associated APC(%) for cancer of the esophagus between 1975-

2010, All Races

Male and Female Male Female

Trend Period Trend Period Trend Period

0.7* 1975-2002 0.7* 1975-1985 0.1 1975-2000

-0.7* 2002-2010 1.2* 1985-1994 -1.5* 2000-2010

0.4* 1994-2005

-1.1* 2005-2010

SURVIVAL & STAGE

Survival can be calculated by different methods for different purposes. The survival statistics presented

here are based on relative survival, which measures the survival of the cancer patients in comparison to the

general population to estimate the effect of cancer. The overall 5-year relative survival for 2003-2009 from 18

SEER geographic areas was 17.3%. Five-year relative survival by race and sex was: 18.5% for white men; 17.2% for

white women; 10.3% for black men; 13.7% for black women.


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Stage Distribution and 5-year Relative Survival by Stage at Diagnosis for

2003-2009, All Races, Both Sexes

Stage at DiagnosisStage

Distribution (%)

5-year

Relative Survival (%)

Localized (confined to primary site) 22 38.6

Regional (spread to regional lymphnodes) 30 20.6

Distant (cancer has metastasized) 36 3.5

Unknown (unstaged) 12 11.2

The stage distribution is based on Summary Stage 2000.

LIFETIME RISK

Based on rates from 2008-2010, 0.51% of men and women born today will be diagnosed with cancer ofthe esophagus at some time during their lifetime. This number can also be expressed as 1 in 198 men and women

will be diagnosed with cancer of the esophagus during their lifetime. These statistics are called the lifetime risk of

developing cancer. Sometimes it is more useful to look at the probability of developing cancer of the esophagus

between two age groups. For example, 0.36% of men will develop cancer of the esophagus between their 50th and

70th birthdays compared to 0.07% for women.

PREVALENCE

On January 1, 2010, in the United States there were approximately 33,839 men and women alive who had

a history of cancer of the esophagus -- 26,388 men and 7,451 women. This includes any person alive on January 1,

2010 who had been diagnosed with cancer of the esophagus at any point prior to January 1, 2010 and includespersons with active disease and those who are cured of their disease. Prevalence can also be expressed as a

percentage and it can also be calculated for a specific amount of time prior to January 1, 2010 such as diagnosed

within 5 years of January 1, 2010.

ACCORDING TO AMERICAN CANCER SOCIETY

Esophageal cancer is a relatively rare form of cancer, with some areas of the world having a markedly

higher rate than others: Belgium, China, Iran, Iceland, India, Japan, the United Kingdom appear to have a higher

incidence, as well as the region around the Caspian Sea. As of 2010 it caused about 395,000 deaths up from

345,000 in 1990.

The American Cancer Society estimated that during 2007, approximately 15,560 new esophageal cancer

cases will be diagnosed in the United States. In the United States, squamous cell carcinoma of the esophagus

usually affects African American males with a history of heavy smoking or alcohol use. Until the 1970s, squamous

cell carcinoma made up the vast majority of esophageal cancers in the United States. In recent decades, incidence

of adenocarcinoma of the esophagus (which is associated with Barrett's esophagus) steadily rose in the United

States to the point that it has now surpassed squamous cell carcinoma in this country. In contrast to squamous cell

carcinoma, esophageal adenocarcinoma is more common in Caucasian men (over the age of 60) than it is in African

Americans. Multiple reports indicate esophageal adenocarcinoma incidence has increased during the past 20


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years, especially in non-Hispanic white men. Esophageal adenocarcinoma age-adjusted incidence increased in New

Mexico from 1973 to 1997. This increase was found in non-Hispanic whites and Hispanics and became

predominant in non-Hispanic whites. Esophageal cancer incidence and mortality rates for African Americans

continue to be higher than the rate for Causasians. However, incidence and mortality of esophageal cancer has

significantly decreased among African Americans since the early 1980s, whereas with Caucasians, it has slightly

increased.

no data

less than 3

3-6

6-9

9-12

12-15

15-18

18-21

21-24

24-27

27-30

30-35

more than 35

Figure. 10. Age-standardised death rates from Esophageal cancer by country

(per 100,000 inhabitants).

SIGNS AND SYMPTOMSIn most cases, cancers of the esophagus are found because of the symptoms they cause. Diagnosis in

people without symptoms is rare and usually accidental (because of tests done to check other medical problems).

Unfortunately, most esophageal cancers do not cause symptoms until they have reached an advanced stage, when

they are harder to treat.

Painful (Odynophagia) or difficult swallowing (Dysphagia)The most common symptom of esophageal cancer is difficulty swallowing, or the sticking of food before it

gets into the stomach. This is usually a progressive problem which begins initially when large pieces of poorly

chewed food are swallowed, but can worsen to the point that thin liquids won't go down easily.

When swallowing becomes difficult, people often change their diet and eating habits without realizing it.

They take smaller bites and chew their food more carefully and slowly. As the cancer grows larger, the problem

gets worse. People then may start eating softer foods that can pass through the esophagus more easily. They may

avoid bread and meat, since these foods typically get stuck. The swallowing problem may even get bad enough

that some people stop eating solid food completely and switch to a liquid diet. If the cancer keeps growing, at

some point even liquids will not be able to pass.

To help pass food through the esophagus, the body makes more saliva. This causes some people to

complain of bringing up lots of thick mucus or saliva.

Notes:

The following groupings were

made:

France includes the overseas

departments as well as

overseas collectivities.

The United Kingdom includes

the Crown dependencies as

well as the overseas territories.

The United States of America

includes the insular areas.

The Netherlands includes Aruba

and the Netherlands Antilles.

Denmark includes Greenland

and the Faroe islands.

China includes the SARs of

Hong Kong and Macao


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Weight lossWeight loss is common and correlates with dysphagia, dietary changes, and tumor-related anorexia.

Weight loss is noted in more than 70% of patients and, if present, carries a worse prognosis.

Pain behind the breastbonePain behind the sternum or in the epigastrium, often of a burning, heartburn-like nature, may be severe,

present itself almost daily, and is worsened by swallowing any form of food.

Cough, hoarseness and hiccupsThe trachea (windpipe) is located directly in front of the esophagus, and it is possible for an esophageal

cancer to erode the entire way through the esophageal wall and into the trachea, creating what is called a

tracheoesophageal (respiratory) fistula This causes cough, an irritating sensation with breathing (especially with

deep breaths). Hoarseness is a result of the tumor affecting the recurrent laryngeal nerve. And hiccups from

phrenic nerve involvement.

Indigestion and HeartburnDue to the reflux of acid and malfunction of the lower esophageal sphincter.

Bleeding manifested by vomiting blood or passing old blood with bowel movementsDue to irritation of the linings of the esophagus and stomach and irritation from the tumor. Over time,

this blood loss can lead to anemia (low red blood cell levels), which may make a person feel tired.

Having one or more of the symptoms above does not mean you have esophageal cancer. In fact, many of

these symptoms are more likely to be caused by other conditions. Still, if you have any of these symptoms,

especially trouble swallowing, it is very important to have them checked by a doctor so that the cause can be

found and treated, if needed.

OTHER MANIFESTING SYMPTOMS OF ESOPHAGEAL CANCER

The clinical presentation of patients with esophageal cancer can be attributed to the direct effects of the

local tumor, regional or distant complications of the disease, or paraneoplastic syndromes.

Symptoms Caused by Local Tumor Effects

Dysphagia Cough and regurgitation Odynophagia Weight loss Upper gastrointestinal bleeding

Symptoms Related to Invasion of Surrounding Structures

Respiratory fistula Hoarseness from recurrent laryngeal nerve invasion Hiccups from phrenic nerve invasion Pain caused by local spread


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Symptoms Related to Distant Disease

Metastatic disease to the lungs, liver, and central nervous system Hypercalcemia

Symptoms related to distant metastasis in the lungs, bone, liver, and central nervous system, particularly

in the case of AC, can also be found at the initial clinical presentation. Hypercalcemia is the most common

paraneoplastic syndrome. In the absence of bone metastases, it is most common in patients with SCC and is

believed to be caused by the production of a parathyroid hormonerelated protein. The physical examination is

often unremarkable, but should be directed toward finding evidence of metastatic disease, including

supraclavicular lymphadenopathy, hepatosplenomegaly, and pleural effusion.

RISK FACTORSA risk factor is anything that changes your chance of getting a disease such as cancer. Different cancers

have different risk factors. For example, smoking is a risk factor for lung cancer, as well as many other types of

cancer.

Scientists have found several risk factors that affect your risk of cancer of the esophagus. Some are more

likely to increase the risk for adenocarcinoma of the esophagus and others for squamous cell carcinoma of the

esophagus.

But risk factors don't tell us everything. Having a risk factor, or even several, does not mean that you will

get the disease. Many people with risk factors never develop esophagus cancer, while others with this disease may

have few or no known risk factors.

AgeThe chance of getting esophageal cancer is low at younger ages and increases with age. Less than 15% of

cases are found in people younger than age 55.

GenderCompared with women, men have more than a 3-fold higher rate of esophageal cancer according to

studies due to their lifestyle especially their smoking habit and drinking alcohol.

Gastroesophageal reflux diseaseIn some people, acid can escape from the stomach into the esophagus. The medical term for this

is Gastroesophageal Reflux Disease (GERD), or just reflux. In many people, reflux causes symptoms such as

heartburn or pain that seem to come from the middle of the chest. In some though, reflux doesn't cause any

symptoms at all.

People with GERD have a higher risk of getting adenocarcinoma of the esophagus. The risk goes up based

on how long the reflux has been going on and how severe the symptoms are. GERD can also cause Barrett's

esophagus, which is linked to an even higher risk.


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Barrett's esophagusIf reflux of stomach acid into the lower esophagus continues for a long time, it can damage the lining of

the esophagus. This causes the squamous cells that usually line the esophagus to be replaced with gland cells.

These gland cells usually look like the cells that line the stomach and the small intestine, and are more resistant to

stomach acid. This condition is known as Barrett's (or Barrett) esophagus.

The longer someone has reflux, the more likely it is that they will develop Barrett's esophagus. Most

people with Barrett's esophagus have had symptoms of "heartburn," but many have no symptoms at all.

Barrett's esophagus increases the risk of adenocarcinoma of the esophagus. This is because the gland cells

in Barrett's esophagus can become more abnormal over time. This can result in dysplasia, a pre-cancerous

condition. Dysplasia is graded by how abnormal the cells look under the microscope. High-grade dysplasia is the

most abnormal and is linked to the highest risk of cancer.

People with Barrett's esophagus are much more likely than people without this condition to develop

esophageal cancer. Still, most people with Barrett's esophagus do not get esophageal cancer. The risk of cancer is

highest if dysplasia is present or if other people in your family also have Barretts.

Tobacco and alcoholThe use of tobacco products, including cigarettes, cigars, pipes, and chewing tobacco, is a major risk factor

for esophageal cancer. The risk goes up with increased use: the more a person uses tobacco and the longer it is

used, the higher the cancer risk. Someone who smokes a pack of cigarettes a day or more has at least twice the

chance of getting adenocarcinoma of the esophagus than a nonsmoker. The link to squamous cell esophageal

cancer is even stronger. The risk of esophageal cancer goes down if tobacco use stops.

Drinking alcohol also increases the risk of esophageal cancer. The chance of getting esophageal cancer

goes up with higher intake of alcohol. Alcohol affects the risk of the squamous cell type more than the risk of

adenocarcinoma.

Combining smoking and drinking alcohol raises the risk of esophageal cancer much more than using either

alone.

ObesityPeople who are overweight or obese (very overweight) have a higher chance of getting adenocarcinoma

of the esophagus. This is in part explained by the fact that people who are obese are more likely to have

esophageal reflux.

DietA diet high in fruits and vegetables is linked to a lower risk of esophageal cancer. The exact reasons for

this are not clear, but fruits and vegetables provide a number of vitamins and minerals that may help prevent

cancer.

On the other hand, certain substances in the diet may increase the cancer risk. For example, there have

been suggestions, as yet unproven, that a diet high in processed meat may increase the chance of developing

esophageal cancer. This may help explain the high rate of this cancer in certain parts of the world.


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Drinking very hot liquids frequently may increase the risk for the squamous cell type of esophageal

cancer. This may be the result of long-term damage the liquids do to the cells lining the esophagus.

Overeating, which leads to obesity, increases the risk of the adenocarcinoma of the esophagus.

AchalasiaIn this condition, the muscle at the lower end of the esophagus (the lower esophageal sphincter) does not

relax properly. Food and liquid that are swallowed have trouble passing into the stomach and tend to collect in the

esophagus, which becomes stretched out (dilated) over time. The cells lining the esophagus can become irritated

from being exposed to foods for longer than normal amounts of time.

People with achalasia have a risk of esophageal cancer that is many times normal. On average, the

cancers are found about 15-20 years after the achalasia is diagnosed.

TylosisThis is a rare, inherited disease that causes excess growth of the top layer of skin on the palms of the

hands and soles of the feet. People with this condition also develop small growths (papillomas) in the esophagus

and have a very high risk of getting squamous cell cancer of the esophagus.

People with tylosis need to be watched closely to try to find esophageal cancer early. Often this requires

regular monitoring with an upper endoscopy.

Esophageal websA web is a thin membrane extending out from the inner lining of the esophagus that causes an area of

narrowing. Most esophageal webs do not cause any problems, but larger webs may cause food to get stuck in the

esophagus, which can lead to problems swallowing.

When an esophageal web is found along with anemia, tongue irritation (glossitis), brittle fingernails, and a

large spleen it is called Plummer-Vinson syndrome. Another name for this is Paterson-Kelly syndrome. About 1 in 10

patients with this syndrome eventually develop squamous cell cancer of the esophagus.

Workplace exposuresExposure to chemical fumes in certain workplaces may lead to an increased risk of esophageal cancer. For

example, exposure to the solvents used for dry cleaning may lead to a greater risk of esophageal cancer. Some

studies have found that dry cleaning workers may have a higher rate of esophageal cancer.

Injury to the esophagusLye is a chemical found in strong industrial and household cleaners such as drain cleaners. Lye is a

corrosive agent, meaning it can burn and destroy cells. Sometimes small children mistakenly drink from a lye-based

cleaner bottle. The lye causes a severe chemical burn in the esophagus. As the injury heals, the scar tissue can

cause an area of the esophagus to become very narrow (called a stricture). People with these strictures have an

increased rate of the squamous cell type of esophageal cancer as adults. The cancers occur on average about 40

years after the lye was swallowed.


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History of certain other cancersPeople who have had certain other cancers, such as lung cancer, mouth cancer, and throat cancer have a

high risk of getting squamous cell carcinoma of the esophagus as well. This may be because all of these cancers can

be caused by smoking.

Human papilloma virusGenes from human papilloma virus (HPV) have been found in up to one-third of esophagus cancer tumors

from patients living in Asia and South Africa. Signs of HPV infection have not been found in esophagus cancers

from patients living in the other areas, including the US.

HPV is a group of more than 100 related viruses. They are called papilloma viruses because some of them

cause a type of growth called a papilloma (or wart). Infection with certain types of HPV is linked to a number of

cancers, including throat cancer, anal cancer, and cervical cancer.

PATHOPHYSIOLOGY

Figure 11. Pathophysiology of Esophageal Cancer

Esophageal cancer arises in the mucosa of the oesophagus. It then progresses locally to invade the

submucosa and the muscular layer, and may invade contiguous structures such as the tracheobronchial tree, the

aorta, or the recurrent laryngeal nerve. Metastasis typically occurs to the peri-esophageal lymph nodes, liver, and

lungs.

The pathophysiological mechanisms of many causes are not yet fully elucidated, and are the subject of

active research. However, mechanisms have been proposed for some of the aetiologic factors especially the

Gastroesophageal Reflux Disease (GERD)and Barretts esophagus.

Gastroesophageal RefluxDisease

Metaplasia

Low Grade Dysplasia

High Grade Dysplasia

Addenocarcinoma


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In this figure, it shows that Chronic GERD causes metaplasia (Barrett's esophagus) in which the stratified

squamous epithelium that normally lines the distal esophagus is replaced by abnormal columnar epithelium.

Although this might seem a favourable adaptation to chronic reflux (because columnar epithelium appears more

resistant to reflux-induced injury), these metaplastic cells may become dysplastic, and ultimately malignant,

through genetic alterations that activate proto-oncogenes and/or disable tumour suppressor genes. Factors that

increase gastro-oesophageal reflux damage, such as hiatus hernia, achalasia, obesity, or medications that lowerthe lower oesophageal sphincter tone, may further increase the risk of esophageal carcinoma.

The progression of Barrett metaplasia to adenocarcinoma is associated with several changes in gene

structure, gene expression, and protein structure.

The oncosuppressor gene TP53 and various oncogenes,

particularly erb -b2, have been studied as potential markers.

Casson and colleagues identified mutations in the TP53 gene in patients with Barrett epithelium

associated with adenocarcinoma. In addition, alterations in p16 genes and cell cycle abnormalities or aneuploidy

appear to be some of the most important and well-characterized molecular changes.

SCREENING AND DIAGNOSIS

Can cancer of the esophagus be found early?

Looking for a disease in someone without symptoms is called screening. The goal of screening is to find a

disease like cancer in an early, more curable stage, in order to help people live longer, healthier lives.

In the United States, screening the general public for esophageal cancer is not recommended by any

professional organization at this time. This is because no screening test has been shown to lower the risk of dying

from esophageal cancer in people who are at average risk.

However, people who have a high risk of esophageal cancer, such as those with Barrett's esophagus, are

often followed closely to look for early cancers and pre-cancers.

Testing for people at high risk

Many experts recommend that people with a high risk of esophageal cancer, such as those with Barrett's

esophagus, have upper endoscopy regularly. For this test, the doctor looks at the inside of the esophagus through

a flexible lighted tube called an endoscope. The doctor may remove small samples of tissue (biopsies) from the

area of Barretts so that they can be checked to see if they contain any abnormal cells (including cancer cells). They

will also get tissue samples from any areas that look more abnormal.

Doctors are not certain how often the test should be repeated, but most recommend testing more often

if areas of abnormal cells (called dysplasia) are found. This testing is repeated even more often if there is high-

grade dysplasia (the cells appear very abnormal).

If the area of Barrett's is large and/or there are many different spots of high-grade dysplasia, surgery to

remove the abnormal area is often advised because of the high risk that an adenocarcinoma is either already

present (but was not found) or will develop within a few years. If treated with surgery, the outlook for these

patients is relatively good.

Surgery may not be an option for some patients if they are in poor health and aren't able to withstand the

operation. Other treatment options for high-grade dysplasia include endoscopic mucosal resection (EMR),

photodynamic therapy (PDT), and radiofrequency ablation.


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Careful monitoring and treatment (if needed) may help prevent some esophageal cancers from

developing. It may also detect some cancers early, when they are more likely to be treated successfully.

DIAGNOSING THE ESOPHAGEAL CANCER

Esophagus cancers are usually found because of signs or symptoms a person is having. If esophagus

cancer is suspected, tests will be needed to confirm the diagnosis.

Medical history and physical examIf you have symptoms that may be caused by esophageal cancer, the doctor will ask about your medical

history to check for possible risk factors and to learn more about your symptoms. Your doctor will also examine

you to look for possible signs of esophageal cancer and other health problems. He or she will probably pay special

attention to your neck and chest areas.

If the results of the exam are abnormal, your doctor will likely order tests to help find the problem. You

may also be referred to a gastroenterologist (a doctor specializing in diseases of digestive tract).

Imaging testsImaging tests use x-rays, magnetic fields, sound waves, or radioactive substances to create pictures of the

inside of your body. Imaging tests may be done for a number of reasons both before and after a diagnosis of

esophageal cancer, including:

To help find a suspicious area that might be cancerousTo learn how far cancer may have spreadTo help determine if treatment has been effectiveTo look for possible signs of cancer recurrence after treatment

Chest X-rayAn x-ray of the organs and bones inside the chest. An x-ray is a type of energy beam that can go

through the body and onto film, making a picture of areas inside the body.

Figure 12. Chest x-ray

Barrium swallowA series of x-rays of the esophagus and stomach. The patient drinks a liquid that contains barium

(a silver-white metallic compound). The liquid coats the esophagus and stomach, and x-rays are taken.

This procedure is also called an upper GI series.


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A barium swallow only shows the shape of the inner lining of the esophagus, so it cannot be used

to determine how far a cancer may have spread outside of the esophagus.

Figure 13. The patient swallows barium liquid and it f lows through the esophagus and into the stomach.

X-rays are taken to look for abnormal areas.

Computed tomography (CT or CAT) scanThe CT scan is a test that uses x-rays to produce detailed cross-sectional images of your body.

Instead of taking one picture, like a standard x-ray does, a CT scanner takes many pictures of the part

of your body being studied as it rotates around you. A computer then combines these pictures into an

image of a slice of your body. Unlike a regular x-ray, a CT scan creates detailed images of the soft

tissues and organs in the body.

CT scans are not usually used to make the initial diagnosis of esophageal cancer, but they can

help see how far it has spread. CT scans often can show where the cancer is in the esophagus. These

scans can also show the nearby organs and lymph nodes (bean-sized collections of immune cells to

which cancers often spread first), as well as distant areas of cancer spread. The CT scan can help todetermine whether surgery is a good treatment option.

Magnetic resonance imaging (MRI) scanLike CT scans, MRI scans provide detailed images of soft tissues in the body. But MRI scans use

radio waves and strong magnets instead of x-rays. The energy from the radio waves is absorbed and

then released in a pattern formed by the type of tissue and by certain diseases. A computer translates

the pattern of radio waves given off by the tissues into a very detailed image of parts of the body. A

Figure 14. CT scan


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contrast material might be injected into a vein. This contrast is different than the one used for CT

scans, so being allergic to one doesnt mean you are allergic to the other.

MRI scans are very helpful in looking at the brain and spinal cord, but they are not often needed

to assess spread of esophageal cancer.

Positron emission tomography (PET) scanFor a PET scan, a form of radioactive sugar (known as fluorodeoxyglucose or FDG) is injected into

the blood. The amount of radioactivity used is very low. Cancer cells in the body are growing rapidly,

so they absorb large amounts of the radioactive sugar. After about an hour, you will be moved onto a

table in the PET scanner. You lie on the table for about 30 minutes while a special camera creates a

picture of areas of radioactivity in the body. The picture is not finely detailed like a CT or MRI scan, but

it provides helpful information about your whole body.

This type of scan may be used to look for possible areas of cancer spread if nothing is found on

other imaging tests.

EndoscopyAn endoscope is a flexible, narrow tube with a video camera and light on the end that is used to look

inside the body. Several tests that use endoscopes can help diagnose esophageal cancer or determine the extent

of its spread.

Figure 15. MRI scan

Figure 16. PET scan


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Upper endoscopyThis is an important test for diagnosing esophageal cancer. During an upper endoscopy, you are

sedated (made sleepy) and then the doctor passes the endoscope down the throat and into the

esophagus and stomach. The camera is connected to a monitor, which lets the doctor see any

abnormal areas in the wall of the esophagus clearly.

The doctor can use special instruments through the scope to remove (biopsy) samples from any

abnormal areas. These samples are sent to the lab so that a doctor can look at them under a

microscope to see if cancer is present.

Upper endoscopy can give the doctor important information about the size and spread of the

tumor, which can be used to help determine if the tumor can be completely removed with surgery.

Endoscopic ultrasoundFor an endoscopic ultrasound, the probe that gives off the sound waves is at the end of an

endoscope, which is passed down the throat and into the esophagus. This allows the probe to get very

close to the cancer. This is done with numbing medicine (local anesthesia) and light sedation.

This test is very useful in determining the size of an esophageal cancer and how far it has grown

into nearby tissues. It can also help determine if nearby lymph nodes might be affected by the cancer. If

enlarged lymph nodes are seen on the ultrasound and not beside the tumor, the doctor may use a thin,

hollow needle to get biopsy samples of them. This helps the doctor decide if the tumor can be surgically

removed.

Figure 17. Upper endoscopy

Figure 18. Endoscopic ultrasound


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BronchoscopyThis exam may be done for cancer in the upper part of the esophagus to see if it has spread to

the windpipe (trachea) or the tubes leading from the trachea into the lung (bronchi). For this test, a

lighted, flexible fiber-optic tube (bronchoscope) is passed through your mouth or nose and down into

the windpipe and bronchi. The mouth and throat are sprayed first with a numbing medicine. You may

also be given medicine through an intravenous (IV) line to make you feel relaxed.

If abnormal areas are seen, small instruments can be passed down the bronchoscope to take

biopsy samples.

Thoracoscopy and laparoscopyThese procedures allow the doctor to see lymph nodes and other organs near the esophagus

inside the chest (by thoracoscopy) or the abdomen (by laparoscopy) through a hollow lighted tube.

These procedures are done in an operating room while you are under general anesthesia (in a

deep sleep). A small cut (incision) is made in the side of the chest wall (for thoracoscopy) or the

abdomen (for laparoscopy). Sometimes more than one cut is made. The doctor then inserts a thin,

lighted tube with a small video camera on the end through the incision to view the space around the

esophagus. The surgeon can pass thin instruments into the space to remove lymph node samples and

take biopsies to see if the cancer has spread. This information is often important in deciding whether or

not a person is likely to benefit from surgery.

Figure 19. Endoscopic ultrasound

Figure 20. Thoracoscopy and laparoscopy


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Lab Testing of biopsy samplesAn area seen on endoscopy or on an imaging test may look like cancer, but the only way to know for sure

is to do a biopsy. For a biopsy, the doctor removes small pieces of tissue from an area that looks abnormal. This

is most often done during an endoscopy exam.

A doctor called apathologistthen looks at the tissue under a microscope to see if any cancer cells arepresent. If there is cancer, the pathologist will determine the type (adenocarcinoma or squamous cell) and the

grade of the cancer (how abnormal the patterns of cells look under the microscope).

HER2 TestingIf esophageal cancer is found but is too advanced for surgery, your biopsy samples may

be tested for the HER2 gene or protein. Some people with esophageal cancer have too much of a

protein called HER2 on the surface of their cancer cells, which helps the cells grow. However, a

drug that targets the HER2 protein, known as trastuzumab (Herceptin), may help treat these

cancers when used along with chemotherapy. Only cancers that have too much of the HER2 gene

or protein are likely to be affected by this drug, which is why doctors may test tumor samples for

it.

Other testsWhen looking for signs of esophageal cancer, a doctor may order a blood test called a complete blood

count (CBC) to look for anemia (which could be caused by internal bleeding). A stool sample may be checked to

see if it contains occult (unseen) blood.

If esophageal cancer is found, the doctor may recommend other tests, especially if surgery may be an

option. For instance, blood tests can be done to make sure your liver and kidney functions are normal. Tests may

also be done to check your lung function, since some people may have lung problems (such as pneumonia) after

surgery. If surgery is planned or you are going to get medicines that may affect the heart, you may also have an

electrocardiogram (EKG) and echocardiogram (ultrasound of the heart) to make sure your heart is functioning

well.

STAGING THE ESOPHAGEAL CANCER

Staging is the process of finding out how far a cancer has spread. The stage of esophageal cancer is a

standard summary of how far the cancer has spread. The treatment and outlook for people with esophageal

cancer depend, to a large extent, on the cancer's stage. Esophageal cancer is staged based on the results of exams,

imaging tests, endoscopies, and biopsies.

Figure 21. Tests for CBC and Stool


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Before the staging systems are introduced, first some background on how cancers grow and spread, and

therefore advance in stage.

There are three ways that cancer spreads in the body.

Through tissue. Cancer invades the surrounding normal tissue. Through the lymph system. Cancer invades the lymph system and travels through the lymph vessels toother places in the body.

Through the blood. Cancer invades the veins and capillaries and travels through the blood toother places in the body.

When cancer cells break away from the primary (original) tumor and travel through the lymph or blood to

other places in the body, another (secondary) tumor may form. This process is called metastasis. The secondary

(metastatic) tumor is the same type of cancer as the primary tumor. For example, if esophageal cancer spreads to

the bones, the cancer cells in the bones are actually esophageal cancer cells. The disease is metastatic esophageal

cancer, not bone cancer.

TNM staging systemThe most common system used to stage esophageal cancer is the TNM system of the American Joint

Committee on Cancer (AJCC). The TNM system is based on several key pieces of information:

T refers to how far the primary tumor has grown into the wall of the esophagus and into nearby organs.Nrefers to cancer spread to nearby lymph nodes.M indicates whether the cancer has metastasized (spread to distant organs).G describes the grade of the cancer, which is based on how the patterns of cancer cells look under amicroscope.

Staging also takes into account the cell type of the cancer (squamous cell carcinoma or adenocarcinoma).

For squamous cell cancers, the location of the tumor can also be a factor in staging.

Figure 22. Staging of Esophageal cancer


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T categories

This describes how deeply the cancer has grown into the wall of the esophagus or into nearby structures.

Most esophageal cancers start in the innermost lining of the esophagus (the epithelium) and then grow into

deeper layers over time.

TX: The primary tumor can't be assessed.

T0: There is no evidence of a primary tumor.Tis: The cancer is only in the epithelium (the top layer of cells lining the inside of the esophagus). It has

not started growing into the deeper layers. This stage is also known as high-grade dysplasia. In the past

it was called carcinoma in situ.

T1: The cancer is growing into the tissue under the epithelium, such as the lamina propria, muscularismucosa, or submucosa.

T1a: The cancer is growing into the lamina propria or muscularis mucosa T1b: The cancer has grown through the other layers and into the submucosa

T2: The cancer is growing into the thick muscle layer (muscularis propria).T3: The cancer is growing into the outer layer of the esophagus (the adventitia).T4: The cancer is growing into nearby structures.

T4a: The cancer is growing into the pleura (the tissue covering the lungs), the pericardium(the tissue covering the heart), or the diaphragm (the thin sheet of muscle below the lungs

that separates the chest from the abdomen). The cancer can be removed with surgery.

T4b: The cancer cannot be removed with surgery because it has grown into the trachea(windpipe), the aorta (the large blood vessel coming from the heart), the spine, or other

crucial structures.

N categories

NX: Nearby lymph nodes can't be assessed.N0: The cancer has not spread to nearby lymph nodes.N1: The cancer has spread to 1 or 2 nearby lymph nodes.N2: The cancer has spread to 3 to 6 nearby lymph nodes.N3: The cancer has spread to 7 or more nearby lymph nodes.

M categories

M0: The cancer has not spread (metastasized) to distant organs or lymph nodes.M1: The cancer has spread to distant lymph nodes and/or other organs.

Grade

The grade of a cancer is based on how normal (or differentiated) the cells look under the microscope. The

higher the number, the more abnormal the cells look. Higher grade tumors tend to grow and spread faster than

lower grade tumors.

GX: The grade cannot be assessed (treated in stage grouping as G1).G1: The cells are well-differentiated.G2: The cells are moderately differentiatedG3: The cells are poorly differentiatedG4: The cells are undifferentiated (these cells are so abnormal that doctors can't tell if they are

adenocarcinoma or squamous cell carcinoma). For staging, G4 cancers are grouped with G3 squamous

cell cancers.


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Location

Some stages of early squamous cell carcinoma also take into account where the tumor is in the

esophagus. The location is assigned as either upper, middle, or lowerbased on where the upper edge of the tumor

is.

STAGE GROUPINGOnce the T, N, M, and G categories have been assigned, this information is combined to assign an overall

stage of 0, I, II, I II, or IV. This process is called stage grouping. Some stages are further subdivided into A, B, or C.

The stages identify cancers that have a similar prognosis (outlook). Patients with lower stage numbers tend to have

a better prognosis.

The stage groupings for squamous cell carcinoma and adenocarcinoma are different. Cancers that have

features of both squamous cell and adenocarcinoma are staged as squamous cell carcinomas.

SQUAMOUS CELL CARCINOMA STAGES

STAGE 0:Tis, N0, M0, GX or G1; any location: This is the earliest stage of esophageal cancer. The cancer cells are found only

in the epithelium(the layer of cells lining the esophagus). The cancer has not grown into the connective tissue

beneath these cells (Tis). The cancer has not spread to lymph nodes (N0) or other organs (M0). This stage is also

called high-grade dysplasia.The tumor is well differentiated (G1) or grade information is not available (GX) and can

be anywhere along the esophagus.

STAGE IA:T1, N0, M0, GX or G1; any location: The cancer has grown from the epithelium into the layers below, such as the

lamina propria, muscularis mucosa, or submucosa, but it has not grown any deeper (T1). It has not spread to lymph

nodes (N0) or to distant sites (M0). The tumor is well differentiated (G1) or grade information is not available (GX).

It can be anywhere along the esophagus.

STAGE IB: EITHER OF THE FOLLOWING:T1, N0, M0, G2 or G3; any location: The cancer has grown from the epithelium into the layers below, such as the

lamina propria, muscularis mucosa, or submucosa, but it has not grown any deeper (T1). It has not spread to lymph

nodes (N0) or to distant sites (M0). It is moderately (G2) or poorly differentiated (G3). The tumor can be anywhere

in the esophagus.

T2 or T3, N0, M0, GX or G1; location lower: The cancer has grown into the muscle layer called the muscularis

propria (T2). It may also have grown through the muscle layer into the adventitia, the connective tissue covering

the outside of the esophagus (T3). The cancer has not spread to lymph nodes (N0) or to distant sites (M0). It is well

differentiated (G1) or grade information is not available (GX). Its highest point is in the lower part of the

esophagus.


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STAGE IIA: EITHER OF THE FOLLOWING:T2 or T3, N0, M0, GX or G1; location upper or middle: The cancer has grown into the muscle layer called the

muscularis propria (T2). It may also have grown through the muscle layer into the adventitia, the connective tissue

covering the outside of the esophagus (T3). The cancer has not spread to lymph nodes (N0) or to distant sites

(M0).The cancer is in the upper or middle part of the esophagus and is well differentiated (G1) or gradeinformation is not available (GX).

T2 or T3, N0, M0, G2 or G3; location lower: The cancer has grown into the muscle layer called the muscularis

propria (T2). It may also have grown through the muscle layer into the adventitia, the connective tissue covering

the outside of the esophagus (T3). The cancer has not spread to lymph nodes (N0) or to distant sites (M0).The

cancer is in the lower part of the esophagus and is moderately (G2) or poorly differentiated (G3).

STAGE IIB: EITHER OF THE FOLLOWING:T2 or T3, N0, M0, G2 or G3; location upper or middle: The cancer has grown into the muscle layer called the

muscularis propria (T2). It may also have grown through the muscle layer into the adventitia, the connective tissuecovering the outside of the esophagus (T3). The cancer has not spread to lymph nodes (N0) or to distant sites (M0).

It is in the upper or middle part of the esophagus and is moderately (G2) or poorly differentiated (G3).

T1 or T2, N1, M0, any G; any location: The cancer has grown into the layers below the epithelium, such as the

lamina propria, muscularis mucosa, or submucosa (T1). It may also have grown into the muscularis propria (T2). It

has not grown through to the outer layer of tissue covering the esophagus. It has spread to 1 or 2 lymph nodes

near the esophagus (N1) but has not spread to lymph nodes further away from the esophagus or to distant sites

(M0). It can be any grade and can be anywhere along the esophagus.

STAGE IIIA: ANY OF THE FOLLOWING:T1 or T2, N2, M0, any G; any location: The cancer has grown into the layers below the epithelium, such as the

lamina propria, muscularis mucosa, or submucosa (T1). It may also have grown into the muscularis propria (T2). It

has not grown through to the outer layer of tissue covering the esophagus. It has spread to 3 to 6 lymph nodes

near the esophagus (N2) but has not spread to lymph nodes farther away from the esophagus or to distant sites

(M0). It can be any grade and can be anywhere along the esophagus.

T3, N1, M0, any G; any location: The cancer has grown through the wall of the esophagus to its outer layer, the

adventitia (T3). It has spread to 1 or 2 lymph nodes near the esophagus (N1), but has not spread to lymph nodes

farther away from the esophagus or to distant sites (M0). It can be any grade and can be anywhere along the

esophagus.

T4a, N0, M0, any G; any location: The cancer has grown all the way through the esophagus and into nearby organs

or tissues (T4a) but still can be removed. It has not spread to nearby lymph nodes (N0) or to distant sites (M0). It

can be any grade and can be anywhere along the esophagus.

STAGE IIIB:


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T3, N2, M0, any G; any location: The cancer has grown through the wall of the esophagus to its outer layer, the

adventitia (T3). It has spread to 3 to 6 lymph nodes near the esophagus (N2), but has not spread to lymph nodes

farther away from the esophagus or to distant sites (M0). It can be any grade and can be anywhere along the

esophagus.

STAGE IIIC: ANY OF THE FOLLOWING:

T4a, N1 or N2, M0, any G; any location: The cancer has grown all the way through the esophagus and into nearby

organs or tissues (T4a) but still can be removed. It has spread to 1 to 6 lymph nodes near the esophagus (N1 or

N2), but has not spread to lymph nodes farther away from the esophagus or to distant sites (M0). It can be any

grade and can be anywhere along the esophagus.

T4b, any N, M0, any G; any location: The cancer cannot be removed with surgery because it has grown into the

trachea (windpipe), the aorta (the large blood vessel coming from the heart), the spine, or other crucial structures

(T4b). It may or may not have spread to nearby lymph nodes (any N), but it has not spread to lymph nodes farther

away from the esophagus or to distant sites (M0). It can be any grade and can be anywhere along the esophagus.

Any T, N3, M0, any G; any location: The cancer has spread to 7 or more nearby lymph nodes (N3), but has not

spread to lymph nodes farther away from the esophagus or to distant sites (M0). It can be any grade and can be

anywhere along the esophagus.

STAGE IV:Any T, any N, M1, any G; any location: The cancer has spread to distant lymph nodes or other sites (M1). It can be

any grade and can be anywhere along the esophagus.

ADENOCARCINOMA STAGES

The location of the cancer along the esophagus does not affect the stage of adenocarcinomas.

STAGE 0:

Tis, N0, M0, GX or G1: This is the earliest stage of esophageal cancer. This stage is also called high-grade dysplasia.

The cancer cells are only found in the epithelium (the layer of cells lining of the esophagus). The cancer has not

grown into the connective tissue beneath these cells. The cancer has not spread to lymph nodes or other organs. It

is well differentiated (G1) or grade information is not available (GX).

STAGE IA:

T1, N0, M0, GX, G1, or G2: The cancer has grown from the epithelium into the layers below, such as the lamina

propria, muscularis mucosa, or submucosa, but it has not grown any deeper (T1). It has not spread to lymph nodes

(N0) or to distant sites (M0). It is well (G1) or moderately differentiated (G2), or grade information is not available

(GX).


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STAGE IB: EITHER OF THE FOLLOWING:

T1, N0, M0, G3: The cancer has grown from the epithelium into the layers below, such as the lamina propria,

muscularis mucosa, or submucosa, but it has not grown any deeper (T1). It has not spread to lymph nodes (N0) or

to distant sites (M0). It is poorly differentiated (G3).

T2, N0, M0, GX, G1, or G2: The cancer has grown into the muscle layer called the muscularis propria (T2). It has not

spread to lymph nodes (N0) or to distant sites (M0). It is well (G1) or moderately differentiated (G2), or grade

information is not available (GX).

STAGE IIA:

T2, N0, M0, G3: The cancer has grown into the muscle layer called the muscularis propria (T2). It has not spread to

lymph nodes (N0) or to distant sites (M0). It is poorly differentiated (G3).

STAGE IIB: EITHER OF THE FOLLOWING:

T3, N0, M0, any G: The cancer has grown through the wall of the esophagus to its outer layer, the adventitia (T3).

It has not spread to lymph nodes (N0) or to distant sites (M0). It can be any grade.

T1 or T2, N1, M0, any G: The cancer has grown into the layers below the epithelium, such as the lamina propria,

muscularis mucosa, or submucosa (T1). It may also have grown into the muscularis propria (T2). It has not grown

through to the outer layer of tissue covering the esophagus. It has spread to 1 or 2 lymph nodes near the

esophagus (N1), but has not spread to lymph nodes farther away from the esophagus or to distant sites (M0). It

can be any grade.

STAGE IIIA: ANY OF THE FOLLOWING:

T1 or T2, N2, M0, any G: The cancer has grown into the layers below the epithelium, such as the lamina propria,

muscularis mucosa, or submucosa (T1). It may also have grown into the muscularis propria (T2). It has not grown

through to the outer layer of tissue covering the esophagus. It has spread to 3 to 6 lymph nodes near the

esophagus (N2) but has not spread to lymph nodes farther away from the esophagus or to distant sites (M0). It can

be any grade.


It has spread to 1 or 2 lymph nodes near the esophagus (N1), but has not spread to lymph nodes farther away from

the esophagus or to distant sites (M0). It can be any grade.

T4a, N0, M0, any G: The cancer has grown all the way through the esophagus and into nearby organs or tissues(T4a) but still can be removed. It has not spread to nearby lymph nodes or to distant sites (M0). It can be any

grade.


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STAGE IIIB:


It has spread to 3 to 6 lymph nodes near the esophagus (N2), but has not spread to lymph nodes farther away from


STAGE IIIC: ANY OF THE FOLLOWING:

T4a, N1 or N2, M0, any G: The cancer has grown all the way through the esophagus and into nearby organs or

tissues (T4a) but still can be removed. It has spread to 1 to 6 lymph nodes near the esophagus (N1 or N2), but has

not spread to lymph nodes farther away from the esophagus or to distant sites (M0). It can be any grade.

T4b, any N, M0, any G: The cancer cannot be removed with surgery because it has grown into the trachea

(windpipe), the aorta (the large blood vessel coming from the heart), the spine, or other crucial structures (T4b). It

may or may not have spread to nearby lymph nodes (any N), but has not spread to lymph nodes farther away from


Any T, N3, M0, any G: The cancer has spread to 7 or more nearby lymph nodes (N3), but has not spread to lymph

nodes farther away from the esophagus or to distant sites (M0). It can be any grade.

STAGE IV:

Any T, any N, M1, any G: The cancer has spread to distant lymph nodes or other sites (M1). It can be any grade.

Figure 23. As esophageal cancer progresses from Stage 0 to Stage IV, the cancer cells grow through the layers of the esophagus

wall and spread to lymph nodes and other organs


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TREATMENTPeople with esophageal cancer have several treatment options. The options are surgery, radiation

therapy, chemotherapy, or a combination of these treatments. For example, radiation therapy and chemotherapy

may be given before or after surgery.

The treatment that is right for you depends mainly on the following:

where the cancer is located within the esophagus whether the cancer has invaded nearby structures whether the cancer has spread to lymph nodes or other organs your symptoms your general health

SIX TYPES OF STANDARD TREATMENT

SurgerySurgery is the most common treatment for cancer of the esophagus.

EsophagectomySurgery to remove some or most of the esophagus is called an esophagectomy. Often a small

part of the stomach is removed as well. The upper part of the esophagus is then connected to the

remaining part of the stomach. Part of the stomach is pulled up into the chest or neck to become the new

esophagus. How much of the esophagus is removed depends upon the stage of the tumor and where it's

located.

Figure 24. Esophagectomy. A portion of the esophagus is removed and the stomach is pulled up and joined to the remaining

esophagus.

The doctor will connect the remaining healthy part of the esophagus to the stomach so the patient can

still swallow. A plastic tube or part of the intestine may be used to make the connection. Lymph nodes near the

esophagus may also be removed and viewed under a microscope to see if they contain cancer. If the esophagus is
http://www.cancer.gov/PublishedContent/MediaLinks/559569.html


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partly blocked by the tumor, an expandable metal stent (tube) may be placed inside the esophagus to help keep it

open.

Figure 25. Esophageal stent. A device (stent) is placed in the esophagus to keep it open to allow food and liquids to pass

through into the stomach.

Lymph node removalFor either type of esophagectomy, nearby lymph nodes are removed during the operation as well.

These are then checked to see if they contain cancer cells. If the cancer has spread to lymph nodes, the

outlook is not as good, and the doctor may recommend other treatments (like chemotherapy and/or

radiation) after surgery.

Risks and side effects of surgery

o A heart attack or a blood clot in the lungs or the brain can occur during or after the operation.Infection is a risk with any surgery.

oLung complications are common. Pneumonia may develop, leading to a longer hospital stay, andsometimes even death.

o After the operation, the stomach may empty too slowly because the nerves that control itscontractions can be affected by surgery. This can, in a few cases, lead to frequent nausea and

vomiting.

o Strictures(narrowing) can form where the esophagus is surgically connected to the stomach,which may cause problems swallowing for some patients.

o After surgery, bile and stomach contents can enter the esophagus because the muscle thatnormally controls this (the lower esophageal sphincter) is often removed or changed by the

surgery. This can cause symptoms such as heartburn.

Radiation therapyRadiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill

cancer cells or keep them from growing. There are two types of radiation therapy. External radiation therapy

uses a machine outside the body to send radiation toward the cancer. Internal radiation therapy uses

a radioactive substance sealed in needles, seeds, wires, or catheters that are placed directly into or near the

cancer. The way the radiation therapy is given depends on the type and stage of the cancer being treated.
http://www.cancer.gov/PublishedContent/MediaLinks/559570.html


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A plastic tube may be inserted into the esophagus to keep it open during radiation therapy. This is

called intraluminal intubation and dilation.

Possible side effects of radiation therapy

o Skin changes ranging from sunburn-like to blistering and open soreso

Nausea and vomitingo Diarrheao Fatigueo Painful sores in the mouth and throato Dry mouth or thick saliva

ChemotherapyChemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing

the cells or by stopping them from dividing. When chemotherapy is taken by mouth or injected into a vein or

muscle, the drugs enter the bloodstream and can reach cancer cells throughout the body (systemic

chemotherapy). When chemotherapy is placed directly into the cerebrospinal fluid, an organ, or a

body cavity such as the abdomen, the drugs mainly affect cancer cells in those areas (regional chemotherapy).The way the chemotherapy is given depends on the type and stage of the cancer being treated.

As part of the main (primary) treatment, along with radiation therapy. Before surgery (usually along with radiation therapy) to try to shrink the cancer and make it

easier to remove. This is called neoadjuvant treatment.

After the cancer has been removed by surgery (usually along with radiation therapy) to try tokill any small areas of tumor cells that may have been left behind. This is known as adjuvant

treatment.

Alone or with radiation to help control symptoms like pain or trouble swallowing when thecancer can't be cured. This is calledpalliative treatment.

Doctors give chemo in cycles, with each period of treatment followed by a rest period to allow the body

time to recover. Each chemo cycle typically lasts for a few weeks.

Many different chemo drugs can be used to treat esophageal cancer. Common regimens are:

Carboplatin and paclitaxel (Taxol) (which may be combined with radiation)oCarboplatinMOA: produces predominantly interstrand DNA cross-links rather than DNA-protein cross-links

oPaclitaxelMOA: a novel antimicrotubule agent that promotes the assembly of microtubules from tubulin

dimers and stabilizes microtubules by preventing depolymerisation

Side effects:

low red blood cell count (anemia) feeling weak or tired hair loss numbness, tingling, or burning in your hands or feet (neuropathy)


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joint and muscle pain nausea and vomiting hypersensitivity reaction - trouble breathing; sudden swelling of your face, lips, tongue,

throat, or trouble swallowing; hives (raised bumps) or rash

Contraindications contraindicated in patients who have a history of hypersensitivity reactions to paclitaxel

or other drugs formulated in polyoxyl 35 castor oil, NF

should not be used in patients with solid tumors who have baseline neutrophil counts of


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Contraindications

contraindicated in patients with baseline neutrophil count < 1500 cells/mm3 not be used in patients with cardiomyopathy and/or heart failure, recent myocardial

infarction, severe arrhythmias

should not be used in patients with hypersensitivity to epirubicin, other anthracyclines, oranthracenediones or severe hepatic dysfunction

DCF: Docetaxel (Taxotere), cisplatin, and 5-FUoDocetaxelMOA: a microtubule inhibitor indicated for single agent for locally advanced or metastatic cancer

oCisplatinMOA: like carboplastin, itproduces predominantly interstrand DNA cross-links rather than DNA-

protein cross-links

o5-fluorouracil (5-FU)MOA: interferes with the synthesis of deoxyribonucleic acid (DNA) and to a lesser extent inhibits

the formation of ribonucleic acid (RNA)

Side effects:

Leukopenia usually follows every course of adequate therapy with fluorouracil hair loss numbness, tingling, or burning in your hands or feet (neuropathy)

Cisplatin with capecitabine (Xeloda)oCisplatinMOA: like carboplastin, itproduces predominantly interstrand DNA cross-links rather than DNA-protein cross-links

oCapecitabine (Xeloda)MOA: combines with enzymes and changes into compounds that are then taken up by cancer

cells where it might be activated into the drug 5-fluorouracil (5-FU)

Side effects:

Mucositis Stomach pain Low appetite, eating little Anemia Dehydration , skin rash or dry, itchy skin

Contraindications:

patients with known dihydropyrimidine dehydrogenase (DPD) deficiency patients with severe renal impairment patients with known hypersensitivity to capecitabine or to any of its components


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Chemoradiation therapyChemoradiation therapy combines chemotherapy and radiation therapy to increase the effects of both.

Possible side effects of chemoradiation therapy

o Nausea and vomitingo

Diarrheao Fatigueo Dry mouth or thick saliva

Laser therapyLaser therapy is a cancer treatment that uses a laser beam (a narrow beam of intense light) to kill cancer

cells.

Possible side effects of laser therapy

o Nausea and vomitingo Diarrheao Fatigue

ElectrocoagulationElectrocoagulation is the use of an electric current to kill cancer cells.

Possible side effects of electrocoagulation therapy

o Nausea and vomitingo Fatigueo Diarrhea

OTHER TREATMENT OPTIONS

Clinical trialsClinical trials are research studies testing the newest cancer treatments and new ways of using existing

cancer treatments. Clinical trials give you a chance to try the latest in cancer treatment, but they can't guarantee a

cure. Ask your doctor if you're eligible to enroll in a clinical trial. Together you can discuss the potential benefits

and risks.

Endoscopic mucosal resectionEndoscopic mucosal resection (EMR) is a technique where the inner lining of the esophagus is removed

with instruments attached to the endoscope. EMR can be used for dysplasia (pre-cancer) and some very early focal

(single, small tumors) cancers of the esophagus.

Photodynamic therapyPhotodynamic therapy(PDT) is a method that can be used to treat esophageal pre-cancer (dysplasia) and

some early esophageal cancers. These may be found when Barrett's esophagus is biopsied. PDT can also be used

to help with symptoms for some cancers that are too advanced to be removed.


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Laser ablationThis technique can be used to help open up the esophagus when it is blocked by an advanced cancer. This

can help improve problems swallowing.

Argon plasma coagulationThis technique is similar to laser ablation, but it uses argon gas and a high-voltage spark delivered through

the tip of an endoscope. The spark causes the gas to reach very high temperatures, which can then be aimed at

the tumor. This approach is used to help unblock the esophagus when the patient has trouble swallowing.

TREATMENT OPTIONS BY STAGE

Patient group Treatment Line Treatment

Stage 0 1st oesophagectomy

2nd endoscopic resection or ablation

Stage 1

Surgical candidate 1st oesophagectomy

Surgical candidate 1st chemoradiotherapy or radiotherapy alone

Not asurgical candidate 2nd endoscopic ablation stenting brachytherapy for symptom relief

Stage 2


Surgical candidate plus preoperative chemoradiotherapy postoperative chemotherapy

Not asurgical candidate 1st chemoradiotherapy or radiotherapy alone


Stage 3


Surgical candidate plus preoperative chemoradiotherapy postoperative chemotherapy

Not asurgical candidate 1st chemoradiotherapy


Stage 4 1st chemotherapy

adjunct radiotherapy

adjunct endoscopic ablation stenting for symptom relief

ALTERNATIVE TREATMENT

Acupuncture

Thin, sterile, stainless steel needles are inserted at specific acupoints on the body that lie in meridians

or channels through which energy, or qi, flows. Stimulation of these points may activate key portions of the

nervous system, resulting in the release of natural pain-killers and a boost to immune cells.

Dietary supplements

Vitamins, minerals, herbs, and botanicals can be powerful adjuncts to any cancer treatment plan, but tell

your doctors which ones you are taking. Some oncologists believe, for instance, that antioxidant supplements like

turmeric negate chemos effectiveness.

Diet Changes

Eating a healthy diet loaded with whole fruits and veggies has a big impact on fighting cancer, says Taryn

Forrelli, ND, a Boston-based naturopath.


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MANAGEMENT

Follow-up care

If you have completed treatment, your doctors will still want to watch you closely. It is very important to

keep all follow-up appointments. During these visits, your doctors will ask about symptoms, examine you, and may

order blood tests, upper endoscopy, or imaging tests such as upper gastrointestinal (GI) x-rays, barium swallows,

or CT scans.

Follow-up is needed to check for cancer recurrence or spread, as well as for possible side effects of certain

treatments. This is the time for you to ask your health care team any questions you need answered and to discuss

any concerns you might have.

Help for trouble swallowing, nutrition, and pain

Palliative treatments are aimed at helping to relieve the symptoms of esophagus cancer, rather than

trying to cure the cancer. In some cases they are used along with other treatments that focus on curing the cancer,

but palliative treatments are often used in people with advanced cancer to help improve their quality of life.

Cancer of the esophagus often causes trouble swallowing. This is why weight loss and weakness due to

poor nutrition are common problems. A team of doctors and nutritionists can work with you to provide nutritionalsupplements and information about your individual nutritional needs. This can be valuable in helping you maintain

your weight and nutritional intake.

Making healthier choices

Eat better or get more exercise. You should also cut down on the alcohol, or give up tobacco. Even things

like keeping your stress level under control may help. Now is a good time to think about making changes that can

have positive effects for the rest of your life. You will feel better and you will also be healthier.

Eating better

If treatment caused weight changes or eating or taste problems, do the best you can and keep in mind

that these problems usually get better over time. You may find it helps to eat small portions every 2 to 3 hours

until you feel better. You may also want to ask your cancer team about seeing a dietician, an expert in nutritionwho can give you ideas on how to deal with these treatment side effects.

Rest, fatigue, and exercise

Extreme tiredness, calledfatigue, is very common in people treated for cancer. This is not a normal

tiredness, but a "bone-weary" exhaustion that doesn't get better with rest. For some people, fatigue lasts a long

time after treatment, and can make it hard for them to exercise and do other things they want to do. But exercise

can help reduce fatigue. Studies have shown that patients who follow an exercise program tailored to their

personal needs feel better physically and emotionally and can cope better, too.

Treatment Options for Recurrent Esophageal Cancer

Use of any standard treatments as palliative therapy to relieve symptoms and improve quality of life. Clinical trials.

PREVENTIONNot all cases of esophageal cancer can be prevented, but the risk of developing this disease can be greatly

reduced by avoiding certain risk factors.


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To prevent new cancers from starting, scientists look at risk factors and protective factors. Anything thatincreases your chance of developing cancer is called a cancer risk factor; anything that decreases your chance of

developing cancer is called a cancer protective factor

You can take steps to reduce your risk of esophageal cancer. For instance:

Quit smoking or chewing tobacco.If you smoke or use chewing tobacco, talk to your doctor about strategies for quitting.

Medications and counseling are available to help you quit. If you don't use tobacco, don't start.

Drink alcohol in moderation, if at all.If you drink, limit yourself to no more than one drink daily if you're a woman or two drinks daily

if you're a man.

Eat more fruits and vegetables.Add a variety of colorful fruits and vegetables to your diet.

Maintain a healthy weight.If you are overweight or obese, talk to your doctor about strategies to help you lose weight. Aim

for a slow and steady weight loss of 1 or 2 pounds a week.

PROGNOSISSurvival in patients with esophageal cancer depends on the stage of the disease. Squamous cell carcinoma

and adenocarcinoma, stage-by-stage, appear to have equivalent survival rates.

Lymph node or solid organ metastases are associated with low survival rates. In 2001-2007, the overall 5-

year survival rate for esophageal cancer was 19%.Patients without lymph node involvement have a significantly

better prognosis and 5-year survival rate than patients with involved lymph nodes. Stage IV lesions are associated

with a 5-year survival rate of less than 5%. (See the table below.)

TNM STAGE 5-YEAR SURVIVAL (%)

0 100

1 80

2A 40

2B 30

3 15

4 0

A report of 1085 patients who underwent transhiatal esophagectomy for cancer showed that the

operation was associated with a 4% operative mortality rate and a 23% 5-year survival rate. A better 5-year

survival rate (48%) was identified in a subgroup of patients who had a complete response (ie, disappearance of the

tumor) following preoperative radiation and chemotherapy (ie, neoadjuvant therapy).

Transhiatal and transthoracic esophagectomies have equivalent long-term survival rates.


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Imaging and prognosis

Suzuki et al found that a higher initial standardized uptake value on positron emission tomography (PET)

scanning is associated with poorer overall survival among patients with esophageal or gastroesophageal carcinoma

receiving chemoradiation. The authors suggested that PET scanning may become useful for individualizing therapy.

A study by Gillies et al also found that PET-computed tomography (CT) scanning can be used to predictsurvival; in this study, the presence of fluorodeoxyglucose (FDG)-avid lymph nodes was an independent adverse

prognostic factor.

HER-2 and prognosis

A study by Prins et al of human epidermal growth factor 2 (HER-2) protein ove

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