Esophageal Cancer
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Esophageal cancer (
American English American English, sometimes called United States English or U.S. English, is the set of variety (linguistics), varieties of the English language native to the United States. English is the Languages of the United States, most widely spoken lang ...
) or oesophageal cancer (
British English British English is the set of Variety (linguistics), varieties of the English language native to the United Kingdom, especially Great Britain. More narrowly, it can refer specifically to the English language in England, or, more broadly, to ...
) is
cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...
arising from the
esophagus The esophagus (American English), oesophagus (British English), or œsophagus (Œ, archaic spelling) (American and British English spelling differences#ae and oe, see spelling difference) all ; : ((o)e)(œ)sophagi or ((o)e)(œ)sophaguses), c ...
—the food pipe that runs between the throat and the stomach. Symptoms often include difficulty in swallowing and weight loss. Other symptoms may include pain when swallowing, a hoarse voice, enlarged lymph nodes ("glands") around the collarbone, a dry cough, and possibly coughing up or vomiting blood. The two main sub-types of the disease are esophageal squamous-cell carcinoma (often abbreviated to ESCC), which is more common in the
developing world A developing country is a sovereign state with a less-developed industrial base and a lower Human Development Index (HDI) relative to developed countries. However, this definition is not universally agreed upon. There is also no clear agreeme ...
, and esophageal
adenocarcinoma Adenocarcinoma (; plural adenocarcinomas or adenocarcinomata ; AC) is a type of cancerous tumor that can occur in several parts of the body. It is defined as neoplasia of epithelial tissue that has glandular origin, glandular characteristics, or ...
(EAC), which is more common in the
developed world A developed country, or advanced country, is a sovereign state that has a high quality of life, developed economy, and advanced technological infrastructure relative to other less industrialized nations. Most commonly, the criteria for eval ...
. A number of less common types also occur. Squamous-cell carcinoma arises from the
epithelial cells Epithelium or epithelial tissue is a thin, continuous, protective layer of cells with little extracellular matrix. An example is the epidermis, the outermost layer of the skin. Epithelial ( mesothelial) tissues line the outer surfaces of man ...
that line the esophagus. Adenocarcinoma arises from
glandular A gland is a cell or an organ in an animal's body that produces and secretes different substances that the organism needs, either into the bloodstream or into a body cavity or outer surface. A gland may also function to remove unwanted substance ...
cells present in the lower third of the esophagus, often where they have already transformed to intestinal cell type (a condition known as
Barrett's esophagus Barrett's esophagus is a condition in which there is an abnormal ( metaplastic) change in the mucosal cells that line the lower part of the esophagus. The cells change from stratified squamous epithelium to simple columnar epithelium, intersper ...
). Causes of the squamous-cell type include
tobacco Tobacco is the common name of several plants in the genus '' Nicotiana'' of the family Solanaceae, and the general term for any product prepared from the cured leaves of these plants. More than 70 species of tobacco are known, but the ...
,
alcohol Alcohol may refer to: Common uses * Alcohol (chemistry), a class of compounds * Ethanol, one of several alcohols, commonly known as alcohol in everyday life ** Alcohol (drug), intoxicant found in alcoholic beverages ** Alcoholic beverage, an alco ...
, very hot drinks, poor diet, and chewing
betel nut The areca nut ( or ) or betel nut () is the fruit of the areca palm ('' Areca catechu''). The palm is originally native to the Philippines, but was carried widely through the tropics by the Austronesian migrations and trade since at least 1 ...
. The most common causes of the adenocarcinoma type are smoking tobacco,
obesity Obesity is a medical condition, considered by multiple organizations to be a disease, in which excess Adipose tissue, body fat has accumulated to such an extent that it can potentially have negative effects on health. People are classifi ...
, and acid reflux. In addition, for patients with
achalasia Esophageal achalasia, often referred to simply as achalasia, is a failure of smooth muscle fibers to relax, which can cause the lower esophageal sphincter to remain closed. Without a modifier, "achalasia" usually refers to achalasia of the esopha ...
,
candidiasis Candidiasis is a fungal infection due to any species of the genus '' Candida'' (a yeast). When it affects the mouth, in some countries it is commonly called thrush. Signs and symptoms include white patches on the tongue or other areas of the ...
(overgrowth of the esophagus with the fungus candida) is the most important risk factor. The disease is diagnosed by
biopsy A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, an interventional radiologist, or an interventional cardiology, interventional cardiologist. The process involves the extraction of sampling (medicine), sample ...
done by an
endoscope An endoscope is an inspection instrument composed of image sensor, optical lens, light source and mechanical device, which is used to look deep into the body by way of openings such as the mouth or anus. A typical endoscope applies several modern ...
(a
fiberoptic An optical fiber, or optical fibre, is a flexible glass or plastic fiber that can transmit light from one end to the other. Such fibers find wide usage in fiber-optic communications, where they permit transmission over longer distances and at ...
camera). Prevention includes stopping smoking and eating a
healthy diet A healthy diet is a diet that maintains or improves overall health. A healthy diet provides the body with essential nutrition: fluid, macronutrients such as protein, micronutrients such as vitamins, and adequate fibre and food energy. A he ...
. Treatment is based on the cancer's stage and location, together with the person's general condition and individual preferences. Small localized squamous-cell cancers may be treated with
surgery Surgery is a medical specialty that uses manual and instrumental techniques to diagnose or treat pathological conditions (e.g., trauma, disease, injury, malignancy), to alter bodily functions (e.g., malabsorption created by bariatric surgery s ...
alone with the hope of a
cure A cure is a substance or procedure that resolves a medical condition. This may include a medication, a surgery, surgical operation, a lifestyle change, or even a philosophical shift that alleviates a person's suffering or achieves a state of heali ...
. In most other cases,
chemotherapy Chemotherapy (often abbreviated chemo, sometimes CTX and CTx) is the type of cancer treatment that uses one or more anti-cancer drugs (list of chemotherapeutic agents, chemotherapeutic agents or alkylating agents) in a standard chemotherapy re ...
with or without
radiation therapy Radiation therapy or radiotherapy (RT, RTx, or XRT) is a therapy, treatment using ionizing radiation, generally provided as part of treatment of cancer, cancer therapy to either kill or control the growth of malignancy, malignant cell (biology), ...
is used along with surgery. Larger tumors may have their growth slowed with chemotherapy and radiation therapy. In the presence of extensive disease or if the affected person is not fit enough to undergo surgery,
palliative care Palliative care (from Latin root "to cloak") is an interdisciplinary medical care-giving approach aimed at optimizing quality of life and mitigating or reducing suffering among people with serious, complex, and often terminal illnesses. Man ...
is often recommended. As of 2018, esophageal cancer was the eighth-most common cancer globally with 572,000 new cases during the year. It caused about 509,000 deaths that year, up from 345,000 in 1990. Rates vary widely among countries, with about half of all cases occurring in China. It is around three times more common in men than in women. Outcomes are related to the extent of the disease and other medical conditions, but generally tend to be fairly poor, as diagnosis is often late.
Five-year survival rates The five-year survival rate is a type of survival rate for estimating the prognosis of a particular disease, normally calculated from the point of diagnosis. Lead time bias from earlier diagnosis can affect interpretation of the five-year surviva ...
are around 13% to 18%.


Signs and symptoms

Prominent symptoms usually do not appear until the cancer has infiltrated over 60% of the circumference of the esophageal tube, by which time the tumor is already in an advanced stage. Onset of symptoms is usually caused by narrowing of the tube due to the physical presence of the tumor. The first and the most common symptom is usually difficulty in swallowing, which is often experienced first with solid foods and later with softer foods and liquids. Pain when swallowing is less usual at first.
Weight loss Weight loss, in the context of medicine, health, or physical fitness, refers to a reduction of the total body mass, by a mean loss of fluid, body fat (adipose tissue), or lean mass (namely bone mineral deposits, muscle, tendon, and other conn ...
is often an initial sign in cases of squamous-cell carcinoma, though not usually in cases of adenocarcinoma. Eventual weight loss due to reduced appetite and
undernutrition Malnutrition occurs when an organism gets too few or too many nutrients, resulting in health problems. Specifically, it is a Deficiency (medicine), deficiency, excess, or imbalance of energy, protein and Vitamin deficiency, other nutrients whic ...
is common.
Pain Pain is a distressing feeling often caused by intense or damaging Stimulus (physiology), stimuli. The International Association for the Study of Pain defines pain as "an unpleasant sense, sensory and emotional experience associated with, or res ...
behind the breastbone or in the region around the stomach often feels like
heartburn Heartburn is a burning sensation felt behind the breastbone. It is a symptom that is commonly linked to acid reflux and is often triggered by food, particularly fatty, sugary, spicy, chocolate, citrus, onion-based and tomato-based products. Ly ...
. The pain can frequently be severe, worsening when food of any sort is swallowed. Another sign may be an unusually husky, raspy, or hoarse-sounding cough, a result of the tumor affecting the
recurrent laryngeal nerve The recurrent laryngeal nerve (RLN), also known as nervus recurrens, is a branch of the vagus nerve ( cranial nerve X) that supplies all the intrinsic muscles of the larynx, with the exception of the cricothyroid muscles. There are two recur ...
. The presence of the tumor may disrupt the normal contractions of the esophagus when swallowing. This can lead to
nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. It can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the throat. Over 30 d ...
and
vomiting Vomiting (also known as emesis, puking and throwing up) is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose. Vomiting can be the result of ailments like food poisoning, gastroenteritis, pre ...
, regurgitation of food and coughing. There is also an increased risk of
aspiration pneumonia Aspiration pneumonia is a type of lung infection that is due to a relatively large amount of material from the stomach or mouth entering the lungs. Signs and symptoms often include fever and cough of relatively rapid onset. Complications may incl ...
due to food entering the airways through the abnormal connections (
fistula In anatomy, a fistula (: fistulas or fistulae ; from Latin ''fistula'', "tube, pipe") is an abnormal connection (i.e. tube) joining two hollow spaces (technically, two epithelialized surfaces), such as blood vessels, intestines, or other h ...
s) that may develop between the esophagus and the
trachea The trachea (: tracheae or tracheas), also known as the windpipe, is a cartilaginous tube that connects the larynx to the bronchi of the lungs, allowing the passage of air, and so is present in almost all animals' lungs. The trachea extends from ...
(windpipe). Early signs of this serious complication may be coughing on drinking or eating. The tumor surface may be fragile and bleed, causing vomiting of blood. Compression of local structures occurs in advanced disease, leading to such problems as upper airway obstruction and
superior vena cava syndrome Superior vena cava syndrome (SVCS), is a group of symptoms caused by obstruction of the superior vena cava ("SVC"), a short, wide vessel carrying circulating blood into the heart. The majority of cases are caused by malignant tumors within the me ...
.
Hypercalcemia Hypercalcemia, also spelled hypercalcaemia, is a high calcium (Ca2+) level in the blood serum. The normal range for total calcium is 2.1–2.6 mmol/L (8.8–10.7 mg/dL, 4.3–5.2 mEq/L), with levels greater than 2.6 mmol/L def ...
(excess calcium in the blood) may occur. If the cancer has spread elsewhere, symptoms related to metastatic disease may appear. Common sites of spread include nearby
lymph node A lymph node, or lymph gland, is a kidney-shaped organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphocytes that includ ...
s, the
liver The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...
,
lungs The lungs are the primary organs of the respiratory system in many animals, including humans. In mammals and most other tetrapods, two lungs are located near the backbone on either side of the heart. Their function in the respiratory syste ...
and bone.
Liver metastasis A liver metastasis is a malignant tumor in the liver that has spread from another organ that is affected by cancer. This can also be called secondary liver cancer or metastatic liver disease. The liver is a common site for metastatic disease becaus ...
can cause
jaundice Jaundice, also known as icterus, is a yellowish or, less frequently, greenish pigmentation of the skin and sclera due to high bilirubin levels. Jaundice in adults is typically a sign indicating the presence of underlying diseases involving ...
and abdominal swelling (
ascites Ascites (; , meaning "bag" or "sac") is the abnormal build-up of fluid in the abdomen. Technically, it is more than 25 ml of fluid in the peritoneal cavity, although volumes greater than one liter may occur. Symptoms may include increased abdo ...
). Lung metastasis can cause, among other symptoms, impaired breathing due to excess fluid around the lungs (
pleural effusion A pleural effusion is accumulation of excessive fluid in the pleural space, the potential space that surrounds each lung. Under normal conditions, pleural fluid is secreted by the parietal pleural capillaries at a rate of 0.6 millilitre per kilog ...
), and
dyspnea Shortness of breath (SOB), known as dyspnea (in AmE) or dyspnoea (in BrE), is an uncomfortable feeling of not being able to breathe well enough. The American Thoracic Society defines it as "a subjective experience of breathing discomfort that ...
(the feelings often associated with impaired breathing).


Causes

The two main types (i.e. squamous-cell carcinoma and
adenocarcinoma Adenocarcinoma (; plural adenocarcinomas or adenocarcinomata ; AC) is a type of cancerous tumor that can occur in several parts of the body. It is defined as neoplasia of epithelial tissue that has glandular origin, glandular characteristics, or ...
) have distinct sets of
risk factor In epidemiology, a risk factor or determinant is a variable associated with an increased risk of disease or infection. Due to a lack of harmonization across disciplines, determinant, in its more widely accepted scientific meaning, is often use ...
s. Squamous-cell carcinoma is linked to lifestyle factors such as smoking and alcohol. Adenocarcinoma has been linked to effects of long-term acid reflux. Tobacco is a risk factor for both types. Both types are more common in people over 60 years of age.


Squamous-cell carcinoma

The two major risk factors for esophageal squamous-cell carcinoma are tobacco (smoking or
chewing Chewing or mastication is the process by which food is crushed and ground by the teeth. It is the first step in the process of digestion, allowing a greater surface area for digestive enzymes to break down the foods. During the mastication proc ...
) and alcohol. The combination of tobacco and alcohol has a strong
synergistic Synergy is an interaction or cooperation giving rise to a whole that is greater than the simple sum of its parts (i.e., a non-linear addition of force, energy, or effect). The term ''synergy'' comes from the Attic Greek word συνεργία ' f ...
effect. Some data suggest that about half of all cases are due to tobacco and about one-third to alcohol, while over three-quarters of the cases in men are due to the combination of smoking and heavy drinking. Risks associated with alcohol appear to be linked to its aldehyde metabolite and to mutations in certain related enzymes. Such metabolic
variants Variant may refer to: Arts and entertainment * ''Variant'' (magazine), a former British cultural magazine * Variant cover, an issue of comic books with varying cover art * ''Variant'' (novel), a novel by Robison Wells * " The Variant", 2021 epis ...
are relatively common in Asia. Other relevant risk factors include regular consumption of very hot drinks (over 65 °C or 149 °F) and ingestion of
caustic Caustic most commonly refers to: * Causticity, the property of being able to corrode organic tissue ** Sodium hydroxide, sometimes called ''caustic soda'' ** Potassium hydroxide, sometimes called ''caustic potash'' ** Calcium oxide, sometimes cal ...
substances. High levels of dietary exposure to
nitrosamines Nitrosamines (or more formally ''N''-nitrosamines) are organic compounds produced by industrial processes. The chemical structure is , where R is usually an alkyl group. Nitrosamines have a nitroso group () that are "probable human carcinogens", ...
(chemical compounds found both in tobacco smoke and certain foodstuffs) also appear to be a relevant risk factor. Unfavorable dietary patterns seem to involve exposure to nitrosamines through processed and barbecued meats, pickled vegetables, etc., and a low intake of fresh foods. Other associated factors include
nutritional deficiencies Malnutrition occurs when an organism gets too few or too many nutrients, resulting in health problems. Specifically, it is a Deficiency (medicine), deficiency, excess, or imbalance of energy, protein and Vitamin deficiency, other nutrients whic ...
, low
socioeconomic status Socioeconomic status (SES) is a measurement used by economics, economists and sociology, sociologsts. The measurement combines a person's work experience and their or their family's access to economic resources and social position in relation t ...
, and poor
oral hygiene Oral hygiene is the practice of keeping one's oral cavity clean and free of disease and other problems (e.g. bad breath) by regular brushing of the teeth (dental hygiene) and adopting good hygiene habits. It is important that oral hygiene be carr ...
. Chewing
betel nut The areca nut ( or ) or betel nut () is the fruit of the areca palm ('' Areca catechu''). The palm is originally native to the Philippines, but was carried widely through the tropics by the Austronesian migrations and trade since at least 1 ...
(areca) is an important risk factor in Asia. Physical trauma may increase the risk. This may include the drinking of very hot drinks.


Adenocarcinoma

Male predominance is particularly strong in esophageal
adenocarcinoma Adenocarcinoma (; plural adenocarcinomas or adenocarcinomata ; AC) is a type of cancerous tumor that can occur in several parts of the body. It is defined as neoplasia of epithelial tissue that has glandular origin, glandular characteristics, or ...
, occurring about 7 to 10 times more frequently in men. This imbalance may be related to the characteristics and interactions of other known risk factors, including acid reflux and
obesity Obesity is a medical condition, considered by multiple organizations to be a disease, in which excess Adipose tissue, body fat has accumulated to such an extent that it can potentially have negative effects on health. People are classifi ...
.


Gastroesophageal reflux disease

The long-term erosive effects of acid reflux (an extremely common condition, also known as
gastroesophageal reflux disease Gastroesophageal reflux disease (GERD) or gastro-oesophageal reflux disease (GORD) is a chronic upper gastrointestinal disease in which stomach content persistently and regularly flows up into the esophagus, resulting in symptoms and/or ...
or GERD) have been strongly linked to this type of cancer. Longstanding GERD can induce a change of cell type in the lower portion of the esophagus in response to erosion of its squamous lining. This phenomenon, known as
Barrett's esophagus Barrett's esophagus is a condition in which there is an abnormal ( metaplastic) change in the mucosal cells that line the lower part of the esophagus. The cells change from stratified squamous epithelium to simple columnar epithelium, intersper ...
, seems to appear about 20 years later in women than in men, possibly due to hormonal factors. At a mechanistic level, in the esophagus there is a small HOXA13 expressing compartment that is more resistant to bile and acids as the normal squamous epithelium and that is prone to both intestinal differentiation as well as oncogenic transformation. Following GERD this HOXA13-expressing compartment outcompetes the normal squamous compartment, leading to the intestinal aspect of the esophagus and increased propensity to the development of esophageal cancer. Having symptomatic GERD or bile reflux makes Barrett's esophagus more likely, which in turn raises the risk of further changes that can ultimately lead to adenocarcinoma. Bile reflux containing unconjugated
bile acids Bile acids are steroid acids found predominantly in the bile of mammals and other vertebrates. Diverse bile acids are synthesized in the liver in peroxisomes. Bile acids are conjugated with taurine or glycine residues to give anions called bile ...
, including deoxycholic acid and chenodeoxycholic acid, appears to contribute to esophageal adenocarcinoma carcinogenesis by inducing
oxidative stress Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage. Disturbances in the normal ...
and DNA damage. The risk of developing adenocarcinoma in the presence of Barrett's esophagus is unclear, and may in the past have been overestimated.


Obesity

Being obese or
overweight Being overweight is having more body fat than is optimally healthy. Being overweight is especially common where food supplies are plentiful and lifestyles are sedentary. , excess weight reached epidemic proportions globally, with more than ...
is strongly associated with risk of developing esophageal adenocarcinoma, and may in fact be the strongest of any type of obesity-related cancer, though the reasons for this remain unclear.
Abdominal obesity Abdominal obesity, also known as central obesity and truncal obesity, is the human condition of an excessive concentration of visceral fat around the stomach and abdomen to such an extent that it is likely to harm its bearer's health. Abdominal ...
seems to be of particular relevance, given the closeness of its association with this type of cancer, as well as with both GERD and Barrett's esophagus. This type of obesity is characteristic of men. Physiologically, it stimulates GERD and also has other chronic inflammatory effects.


Helicobacter pylori

''
Helicobacter pylori ''Helicobacter pylori'', previously known as ''Campylobacter pylori'', is a gram-negative, Flagellum#bacterial, flagellated, Bacterial cellular morphologies#Helical, helical bacterium. Mutants can have a rod or curved rod shape that exhibits l ...
'' infection (a common occurrence thought to have affected over half of the world's population) is not a risk factor for esophageal adenocarcinoma and actually appears to be protective. Despite being a cause of GERD and a risk factor for
gastric cancer Stomach cancer, also known as gastric cancer, is a malignant tumor of the stomach. It is a cancer that develops in the lining of the stomach. Most cases of stomach cancers are gastric carcinomas, which can be divided into a number of subtypes ...
, the infection seems to be associated with a reduced risk of esophageal adenocarcinoma of as much as 50%. The biological explanation for a protective effect is somewhat unclear. One explanation is that some strains of ''H. pylori'' reduce
stomach acid Gastric acid or stomach acid is the acidic component – hydrochloric acid – of gastric juice, produced by parietal cells in the gastric glands of the stomach lining. In humans, the pH is between one and three, much lower than most other an ...
, thereby reducing damage by GERD. Decreasing rates of ''H. pylori'' infection in Western populations over recent decades, which have been linked to less overcrowding in households, could be a factor in the concurrent increase in esophageal adenocarcinoma.


Other risk factors for esophageal adenocarcinoma

Female hormones may also have a protective effect, as EAC is not only much less common in women but develops later in life, by an average of 20 years. Although studies of many reproductive factors have not produced a clear picture, risk seems to decline for the mother in line with prolonged periods of
breastfeeding Breastfeeding, also known as nursing, is the process where breast milk is fed to a child. Infants may suck the milk directly from the breast, or milk may be extracted with a Breast pump, pump and then fed to the infant. The World Health Orga ...
. Tobacco smoking increases risk, but the effect in esophageal adenocarcinoma is slight compared to that in squamous cell carcinoma, and alcohol has not been demonstrated to be a cause.


Related conditions

*
Head and neck cancer Head and neck cancer is a general term encompassing multiple cancers that can develop in the head and neck region. These include cancers of the mouth, tongue, gums and lips (oral cancer), voice box ( laryngeal), throat ( nasopharyngeal, orophary ...
is associated with second
primary tumor A primary tumor is a tumor growing at the anatomical site where tumor progression began and proceeded to yield a cancerous mass. Most solid cancers develop at their primary site but may then go on to metastasize or spread to other parts of the b ...
s in the region, including esophageal squamous-cell carcinomas, due to field cancerization (i.e. a regional reaction to long-term
carcinogen A carcinogen () is any agent that promotes the development of cancer. Carcinogens can include synthetic chemicals, naturally occurring substances, physical agents such as ionizing and non-ionizing radiation, and biologic agents such as viruse ...
ic exposure). * History of
radiation therapy Radiation therapy or radiotherapy (RT, RTx, or XRT) is a therapy, treatment using ionizing radiation, generally provided as part of treatment of cancer, cancer therapy to either kill or control the growth of malignancy, malignant cell (biology), ...
for other conditions in the
chest The thorax (: thoraces or thoraxes) or chest is a part of the anatomy of mammals and other tetrapod animals located between the neck and the abdomen. In insects, crustaceans, and the extinct trilobites, the thorax is one of the three main di ...
is a risk factor for esophageal adenocarcinoma. * Corrosive injury to the esophagus by accidentally or intentionally swallowing
caustic Caustic most commonly refers to: * Causticity, the property of being able to corrode organic tissue ** Sodium hydroxide, sometimes called ''caustic soda'' ** Potassium hydroxide, sometimes called ''caustic potash'' ** Calcium oxide, sometimes cal ...
substances is a risk factor for squamous cell carcinoma. * Tylosis with esophageal cancer is a rare familial disease with autosomal dominant inheritance that has been linked to a mutation in the '' RHBDF2'' gene, present on chromosome 17: it involves thickening of the skin of the palms and soles and a high lifetime risk of squamous cell carcinoma. *
Achalasia Esophageal achalasia, often referred to simply as achalasia, is a failure of smooth muscle fibers to relax, which can cause the lower esophageal sphincter to remain closed. Without a modifier, "achalasia" usually refers to achalasia of the esopha ...
(i.e. lack of the involuntary reflex in the esophagus after swallowing) appears to be a risk factor for both main types of esophageal cancer, at least in men, due to stagnation of trapped food and drink. * Plummer–Vinson syndrome (a rare disease that involves esophageal webs) is also a risk factor. * There is some evidence suggesting a possible causal association between
human papillomavirus Human papillomavirus infection (HPV infection) is caused by a DNA virus from the ''Papillomaviridae'' family. Many HPV infections cause no symptoms and 90% resolve spontaneously within two years. In some cases, an HPV infection persists and r ...
(HPV) and esophageal squamous-cell carcinoma. The relationship is unclear. Possible relevance of HPV could be greater in places that have a particularly high incidence of this form of the disease, as in some Asian countries, including China. * There is an association between
celiac disease Coeliac disease (British English) or celiac disease (American English) is a long-term autoimmune disorder, primarily affecting the small intestine. Patients develop intolerance to gluten, which is present in foods such as wheat, rye, spel ...
and esophageal cancer. People with untreated celiac disease have a higher risk, but this risk decreases with time after diagnosis, probably due to the adoption of a
gluten-free diet A gluten-free diet (GFD) is a nutritional plan that strictly excludes gluten, which is a mixture of prolamin proteins found in wheat (and all of its species and hybrids, such as spelt, kamut, and triticale), as well as barley, rye, and oats ...
, which seems to have a protective role against development of malignancy in people with celiac disease. However, the delay in diagnosis and initiation of a gluten-free diet seems to increase the risk of malignancy. Moreover, in some cases the detection of celiac disease is due to the development of cancer, whose early symptoms are similar to some that may appear in celiac disease.


Diagnosis


Clinical evaluation

Although an occlusive tumor may be suspected on a
barium swallow An upper gastrointestinal series, also called a barium swallow, barium study, or barium meal, is a series of radiographs used to examine the gastrointestinal tract for abnormalities. A contrast medium, usually a radiocontrast agent such as bariu ...
or barium meal, the diagnosis is best made with an examination using an
endoscope An endoscope is an inspection instrument composed of image sensor, optical lens, light source and mechanical device, which is used to look deep into the body by way of openings such as the mouth or anus. A typical endoscope applies several modern ...
. This involves the passing of a flexible tube with a light and camera down the esophagus and examining the wall, and is called an esophagogastroduodenoscopy. Biopsies taken of suspicious lesions are then examined
histologically Histology, also known as microscopic anatomy or microanatomy, is the branch of biology that studies the microscopic anatomy of biological tissue (biology), tissues. Histology is the microscopic counterpart to gross anatomy, which looks at large ...
for signs of malignancy. Additional testing is needed to assess how much the cancer has spread (see , below).
Computed tomography A computed tomography scan (CT scan), formerly called computed axial tomography scan (CAT scan), is a medical imaging technique used to obtain detailed internal images of the body. The personnel that perform CT scans are called radiographers or ...
(CT) of the chest, abdomen and pelvis can evaluate whether the cancer has spread to adjacent tissues or distant organs (especially
liver The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...
and
lymph node A lymph node, or lymph gland, is a kidney-shaped organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphocytes that includ ...
s). The sensitivity of a CT scan is limited by its ability to detect masses (e.g. enlarged
lymph node A lymph node, or lymph gland, is a kidney-shaped organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphocytes that includ ...
s or involved organs) generally larger than 1 cm.
Positron emission tomography Positron emission tomography (PET) is a functional imaging technique that uses radioactive substances known as radiotracers to visualize and measure changes in metabolic processes, and in other physiological activities including blood flow, r ...
is also used to estimate the extent of the disease and is regarded as more precise than CT alone. PET/MR as a novel modality has shown promising results in preoperative staging with fair feasibility and good correlation in comparison to PET/CT. It can enhance tissue differentiation with lowering the radiation dose to the patient. Esophageal endoscopic ultrasound can provide staging information regarding the level of tumor invasion, and possible spread to regional lymph nodes. The location of the tumor is generally measured by the distance from the teeth. The esophagus (25 cm or 10 in long) is commonly divided into three parts for purposes of determining the location. Adenocarcinomas tend to occur nearer the stomach and squamous cell carcinomas nearer the throat, but either may arise anywhere in the esophagus. File:Barretts esophagus.jpg, Endoscopic image of Barrett esophagus – a frequent precursor of esophageal adenocarcinoma File:Mid esophageal mass.jpg, Endoscopy and radial endoscopic ultrasound images of a submucosal tumor in the central portion of the esophagus File:Tumor Esophagus.JPG,
Contrast CT Contrast CT, or contrast-enhanced computed tomography (CECT), is CT scan, X-ray computed tomography (CT) using radiocontrast. Radiocontrasts for X-ray CT are generally Iodinated contrast, iodine-based types. This is useful to highlight structure ...
scan showing an esophageal tumor (axial view) File:Tumor Esophagus2.JPG, Contrast CT scan showing an esophageal tumor (coronal view) File:EsoCaSagMark.png, Esophageal cancer File:Esophageal adenocarcinoma - intermed mag.jpg,
Micrograph A micrograph is an image, captured photographically or digitally, taken through a microscope or similar device to show a magnify, magnified image of an object. This is opposed to a macrograph or photomacrograph, an image which is also taken ...
showing
histopathological Histopathology (compound of three Greek language, Greek words: 'tissue', 'suffering', and ''-logy, -logia'' 'study of') is the light microscope, microscopic examination of Tissue (biology), tissue in order to study the manifestations of dis ...
appearance of an esophageal adenocarcinoma (dark blue – upper-left of image) and normal squamous epithelium (upper-right of image) at
H&E stain Hematoxylin and eosin stain ( or haematoxylin and eosin stain or hematoxylin–eosin stain; often abbreviated as H&E stain or HE stain) is one of the principal tissue stains used in histology. It is the most widely used stain in medical diag ...
ing


Types

Esophageal cancers are typically
carcinoma Carcinoma is a malignancy that develops from epithelial cells. Specifically, a carcinoma is a cancer that begins in a tissue that lines the inner or outer surfaces of the body, and that arises from cells originating in the endodermal, mesoder ...
s that arise from the
epithelium Epithelium or epithelial tissue is a thin, continuous, protective layer of cells with little extracellular matrix. An example is the epidermis, the outermost layer of the skin. Epithelial ( mesothelial) tissues line the outer surfaces of man ...
, or surface lining, of the esophagus. Most esophageal cancers fall into one of two classes: esophageal squamous-cell carcinomas (ESCC), which are similar to
head and neck cancer Head and neck cancer is a general term encompassing multiple cancers that can develop in the head and neck region. These include cancers of the mouth, tongue, gums and lips (oral cancer), voice box ( laryngeal), throat ( nasopharyngeal, orophary ...
in their appearance and association with tobacco and alcohol consumption—and esophageal adenocarcinomas (EAC), which are often associated with a history of GERD and Barrett's esophagus. A rule of thumb is that a cancer in the upper two-thirds is likely to be ESCC and one in the lower one-third EAC. Rare histologic types of esophageal cancer include different variants of squamous-cell carcinoma, and non-epithelial tumors, such as leiomyosarcoma, malignant melanoma,
rhabdomyosarcoma Rhabdomyosarcoma (RMS) is a highly aggressive form of cancer that develops from mesenchymal cells that have failed to fully differentiate into myocytes of skeletal muscle. Cells of the neoplasm, tumor are identified as rhabdomyoblasts. The four ...
and
lymphoma Lymphoma is a group of blood and lymph tumors that develop from lymphocytes (a type of white blood cell). The name typically refers to just the cancerous versions rather than all such tumours. Signs and symptoms may include enlarged lymph node ...
, among others.


Staging

Staging is based on the
TNM staging system The TNM Classification of Malignant Tumors (TNM) is a globally recognised standard for classifying the anatomical extent of the spread of malignant tumours (cancer). It has gained wide international acceptance for many solid tumor cancers, but is ...
, which classifies the amount of tumor invasion (T), involvement of
lymph nodes A lymph node, or lymph gland, is a kidney-shaped Organ (anatomy), organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphoc ...
(N), and distant
metastasis Metastasis is a pathogenic agent's spreading from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, ...
(M). The currently preferred classification is the 2010 AJCC staging system for cancer of the esophagus and the esophagogastric junction. To help guide clinical decision making, this system also incorporates information on cell type (ESCC, EAC, etc.), grade (degree of differentiation – an indication of the biological aggressiveness of the cancer cells), and tumor location (upper, middle, lower, or junctional). File:Diagram showing T1,T2 and T3 stages of oesophageal cancer CRUK 277.svg, T1, T2, and T3 stages of esophageal cancer File:Diagram showing stage T4 oesophagus cancer CRUK 271.svg, Stage T4 esophageal cancer File:Diagram showing oesophageal cancer in the lymph nodes (N staging) CRUK 174.svg, Esophageal cancer with spread to lymph nodes


Prevention

Prevention includes stopping smoking or chewing tobacco. Overcoming addiction to areca chewing in Asia is another promising strategy for the prevention of esophageal squamous-cell carcinoma. The risk can also be reduced by maintaining a normal body weight. According to a 2022 umbrella review, calcium intake could be associated with lower risk. According to the
National Cancer Institute The National Cancer Institute (NCI) coordinates the United States National Cancer Program and is part of the National Institutes of Health (NIH), which is one of eleven agencies that are part of the U.S. Department of Health and Human Services. ...
, "diets high in cruciferous (cabbage, broccoli/broccolini, cauliflower, Brussels sprouts) and green and yellow vegetables and fruits are associated with a decreased risk of esophageal cancer."
Dietary fiber Dietary fiber (fibre in English in the Commonwealth of Nations, Commonwealth English) or roughage is the portion of plant-derived food that cannot be completely broken down by human digestive enzymes. Dietary fibers are diverse in chemical co ...
is thought to be protective, especially against esophageal adenocarcinoma. There is no evidence that vitamin supplements change the risk.


Screening

People with
Barrett's esophagus Barrett's esophagus is a condition in which there is an abnormal ( metaplastic) change in the mucosal cells that line the lower part of the esophagus. The cells change from stratified squamous epithelium to simple columnar epithelium, intersper ...
(an abnormality of the cells lining the lower esophagus) are at much higher risk, and may receive regular endoscopic screening for the early signs of cancer. Because the benefit of screening for adenocarcinoma in people without symptoms is unclear, it is not recommended in the United States. The Nath Score is a history-based risk assessment model developed using machine learning and retrospective data. It evaluates clinical history and symptom patterns to estimate the likelihood of esophageal cancer and has been proposed as a screening tool, particularly in settings where access to endoscopic screening is limited. While retrospective studies support its ability to identify high-risk individuals, it has not yet been adopted into standard screening guidelines.


Management

Treatment is best managed by a multidisciplinary team covering the various specialties involved. Adequate
nutrition Nutrition is the biochemistry, biochemical and physiology, physiological process by which an organism uses food and water to support its life. The intake of these substances provides organisms with nutrients (divided into Macronutrient, macro- ...
must be assured, and appropriate dental care is essential. Factors that influence treatment decisions include the stage and cellular type of cancer (EAC, ESCC, and other types), along with the person's general condition and any other diseases that are present. In general, treatment with a curative intention is restricted to localized disease, without distant
metastasis Metastasis is a pathogenic agent's spreading from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, ...
: in such cases a combined approach that includes surgery may be considered. Disease that is widespread, metastatic or recurrent is managed palliatively: in this case, chemotherapy may be used to lengthen survival, while treatments such as
radiotherapy Radiation therapy or radiotherapy (RT, RTx, or XRT) is a treatment using ionizing radiation, generally provided as part of cancer therapy to either kill or control the growth of malignant cells. It is normally delivered by a linear particle ...
or
stent In medicine, a stent is a tube usually constructed of a metallic alloy or a polymer. It is inserted into the Lumen (anatomy), lumen (hollow space) of an anatomic vessel or duct to keep the passageway open. Stenting refers to the placement of ...
ing may be used to relieve symptoms and make it easier to swallow.


Surgery

If the cancer has been diagnosed while still in an early stage, surgical treatment with a curative intention may be possible. Some small tumors that only involve the
mucosa A mucous membrane or mucosa is a membrane that lines various cavities in the body of an organism and covers the surface of internal organs. It consists of one or more layers of epithelial cells overlying a layer of loose connective tissue. It ...
or lining of the esophagus may be removed by endoscopic mucosal resection (EMR). Otherwise, curative surgery of early-stage lesions may entail removal of all or part of the esophagus (
esophagectomy Esophagectomy or oesophagectomy is the surgical removal of all or parts of the esophagus. Medical uses The principal objective is to remove the esophagus, a part of the gastrointestinal tract. This procedure is usually done for patients with es ...
), although this is a difficult operation with a relatively high risk of mortality or post-operative difficulties. The benefits of surgery are less clear in early-stage ESCC than EAC. There are a number of surgical options, and the best choices for particular situations remain the subject of research and discussion. Online edition, with updates to 2014 The likely
quality of life Quality of life (QOL) is defined by the World Health Organization as "an individual's perception of their position in life in the context of the culture and value systems in which they live and in relation to their goals, expectations, standards ...
after treatment is a relevant factor when considering surgery. Surgical outcomes are likely better in large centers where the procedures are frequently performed. If the cancer has spread to other parts of the body, esophagectomy is nowadays not normally performed. Esophagectomy is the removal of a segment of the esophagus; as this shortens the length of the remaining esophagus, some other segment of the digestive tract is pulled up through the chest cavity and interposed. This is usually the
stomach The stomach is a muscular, hollow organ in the upper gastrointestinal tract of Human, humans and many other animals, including several invertebrates. The Ancient Greek name for the stomach is ''gaster'' which is used as ''gastric'' in medical t ...
or part of the
large intestine The large intestine, also known as the large bowel, is the last part of the gastrointestinal tract and of the Digestion, digestive system in tetrapods. Water is absorbed here and the remaining waste material is stored in the rectum as feces befor ...
(colon) or
jejunum The jejunum is the second part of the small intestine in humans and most higher vertebrates, including mammals, reptiles, and birds. Its lining is specialized for the absorption by enterocytes of small nutrient molecules which have been pr ...
. Reconnection of the stomach to a shortened esophagus is called an esophagogastric
anastomosis An anastomosis (, : anastomoses) is a connection or opening between two things (especially cavities or passages) that are normally diverging or branching, such as between blood vessels, leaf veins, or streams. Such a connection may be normal (su ...
. Esophagectomy can be performed using several methods. The choice of the surgical approach depends on the characteristics and location of the tumor, and the preference of the surgeon. Clear evidence from clinical trials for which approaches give the best outcomes in different circumstances is lacking. A first decision, regarding the point of entry, is between a transhiatial and a transthoracic procedure. The more recent transhiatial approach avoids the need to open the chest; instead the surgeon enters the body through an incision in the lower abdomen and another in the neck. The lower part of the esophagus is freed from the surrounding tissues and cut away as necessary. The stomach is then pushed through the esophageal hiatus (the hole where the esophagus passes through the diaphragm) and is joined to the remaining upper part of the esophagus at the neck. The traditional transthoracic approach enters the body through the chest, and has a number of variations. The thoracoabdominal approach opens the abdominal and thoracic cavities together, the two-stage Ivor Lewis (also called Lewis–Tanner) approach involves an initial
laparotomy A laparotomy is a surgical procedure involving a surgical incision through the abdominal wall to gain access into the abdominal cavity. It is also known as a celiotomy. Origins and history The first successful laparotomy was performed without ...
and construction of a gastric tube, followed by a right thoracotomy to excise the tumor and create an esophagogastric anastomosis. The three-stage McKeown approach adds a third incision in the neck to complete the cervical anastomosis. Recent approaches by some surgeons use what is called extended esophagectomy, where more surrounding tissue, including
lymph nodes A lymph node, or lymph gland, is a kidney-shaped Organ (anatomy), organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphoc ...
, is removed ''en bloc''. If the person cannot swallow at all, an esophageal stent may be inserted to keep the esophagus open;
stent In medicine, a stent is a tube usually constructed of a metallic alloy or a polymer. It is inserted into the Lumen (anatomy), lumen (hollow space) of an anatomic vessel or duct to keep the passageway open. Stenting refers to the placement of ...
s may also assist in occluding fistulas. A
nasogastric tube Nasogastric intubation is a medical process involving the insertion of a plastic tube (nasogastric tube or NG tube) through the nose, down the esophagus, and down into the stomach. Orogastric intubation is a similar process involving the insertion ...
may be necessary to continue feeding while treatment for the tumor is given, and some patients require a
gastrostomy A gastrostomy is the creation of an artificial external opening into the stomach for nutritional support or gastric decompression. Typically this would include an incision in the patient's epigastrium as part of a formal operation. When originall ...
(feeding hole in the skin that gives direct access to the stomach). The latter two are especially important if the patient tends to aspirate food or saliva into the airways, predisposing for
aspiration pneumonia Aspiration pneumonia is a type of lung infection that is due to a relatively large amount of material from the stomach or mouth entering the lungs. Signs and symptoms often include fever and cough of relatively rapid onset. Complications may incl ...
.


Chemotherapy and radiotherapy

Chemotherapy Chemotherapy (often abbreviated chemo, sometimes CTX and CTx) is the type of cancer treatment that uses one or more anti-cancer drugs (list of chemotherapeutic agents, chemotherapeutic agents or alkylating agents) in a standard chemotherapy re ...
depends on the tumor type, but tends to be
cisplatin Cisplatin is a chemical compound with chemical formula, formula ''cis''-. It is a coordination complex of platinum that is used as a chemotherapy medication used to treat a number of cancers. These include testicular cancer, ovarian cancer, c ...
-based (or
carboplatin Carboplatin, sold under the brand name Paraplatin among others, is a chemotherapy medication used to treat a number of forms of cancer. This includes ovarian cancer, lung cancer, head and neck cancer, brain cancer, and neuroblastoma. It is a ...
or
oxaliplatin Oxaliplatin, sold under the brand name Eloxatin among others, is a cancer medication (platinum-based antineoplastic class) used to treat colorectal cancer. It is given by intravenous, infusion into a vein. Common side effects include paresth ...
) every three weeks with fluorouracil (5-FU) or
capecitabine Capecitabine, sold under the brand name Xeloda among others, is a anticancer medication used to treat breast cancer, gastric cancer and colorectal cancer. For breast cancer it is often used together with docetaxel. It is taken by mouth. ...
either continuously or every three weeks. In more studies, addition of epirubicin was better than other three drug regimens in advanced nonresectable cancer. However, a meta-analysis in 2017 failed to demonstrate that
anthracyclines Anthracyclines are a class of drugs used in cancer chemotherapy that are extracted from '' Streptomyces peucetius'' bacterium. These compounds are used to treat many cancers, including leukemias, lymphomas, breast, stomach, uterine, ovarian, b ...
such as epiribicin improved survival. Therefore in metastatic cancer, a two drug combination is now standard. Most recently with the addition of nivolumab or pembrolizumab
immunotherapy Immunotherapy or biological therapy is the treatment of disease by activating or suppressing the immune system. Immunotherapies designed to elicit or amplify an immune response are classified as ''activation immunotherapies,'' while immunotherap ...
where molecular markers suggest these may be helpful.
Chemotherapy Chemotherapy (often abbreviated chemo, sometimes CTX and CTx) is the type of cancer treatment that uses one or more anti-cancer drugs (list of chemotherapeutic agents, chemotherapeutic agents or alkylating agents) in a standard chemotherapy re ...
may be given after surgery (adjuvant, i.e. to reduce risk of recurrence), before surgery (neoadjuvant) or if surgery is not possible.
Cisplatin Cisplatin is a chemical compound with chemical formula, formula ''cis''-. It is a coordination complex of platinum that is used as a chemotherapy medication used to treat a number of cancers. These include testicular cancer, ovarian cancer, c ...
and fluorouracil were most commonly used a, however the REAL-2 trial confirmed that
oxaliplatin Oxaliplatin, sold under the brand name Eloxatin among others, is a cancer medication (platinum-based antineoplastic class) used to treat colorectal cancer. It is given by intravenous, infusion into a vein. Common side effects include paresth ...
and
capecitabine Capecitabine, sold under the brand name Xeloda among others, is a anticancer medication used to treat breast cancer, gastric cancer and colorectal cancer. For breast cancer it is often used together with docetaxel. It is taken by mouth. ...
were non-inferior and potentially more convenient.
Radiotherapy Radiation therapy or radiotherapy (RT, RTx, or XRT) is a treatment using ionizing radiation, generally provided as part of cancer therapy to either kill or control the growth of malignant cells. It is normally delivered by a linear particle ...
is given before, during, or after chemotherapy or surgery, and sometimes on its own to control symptoms. In patients with localized disease but contraindications to surgery, "radical radiotherapy" may be used with curative intent.


Other approaches

Forms of endoscopic therapy have been used for stage 0 and I disease: endoscopic mucosal resection (EMR) and mucosal ablation using radiofrequency ablation, photodynamic therapy, Nd-YAG laser, or argon plasma coagulation.
Laser A laser is a device that emits light through a process of optical amplification based on the stimulated emission of electromagnetic radiation. The word ''laser'' originated as an acronym for light amplification by stimulated emission of radi ...
therapy is the use of high-intensity light to destroy tumor cells while affecting only the treated area. This is typically done if the cancer cannot be removed by surgery. The relief of a blockage can help with pain and difficulty swallowing.
Photodynamic therapy Photodynamic therapy (PDT) is a form of phototherapy involving light and a photosensitizing chemical substance used in conjunction with molecular oxygen to elicit cell death ( phototoxicity). PDT is used in treating acne, wet age-related macula ...
, a type of laser therapy, involves the use of drugs that are absorbed by cancer cells; when exposed to a special light, the drugs become active and destroy the cancer cells. File:Diagram showing internal radiotherapy for cancer of the oesophagus CRUK 162.svg, Internal radiotherapy for esophageal cancer File:SEMS endo.jpg, Self-expandable metallic stents are sometimes used for
palliative care Palliative care (from Latin root "to cloak") is an interdisciplinary medical care-giving approach aimed at optimizing quality of life and mitigating or reducing suffering among people with serious, complex, and often terminal illnesses. Man ...


Follow-up

Patients are followed closely after a treatment regimen has been completed. Frequently, other treatments are used to improve symptoms and maximize nutrition.


Prognosis

In general, the prognosis of esophageal cancer is quite poor, because most patients present with advanced disease. By the time the first symptoms (such as difficulty swallowing) appear, the disease has already progressed. The overall
five-year survival rate The five-year survival rate is a type of survival rate for estimating the prognosis of a particular disease, normally calculated from the point of diagnosis. Lead time bias from earlier diagnosis can affect interpretation of the five-year surv ...
(5YSR) in the United States is around 15%, and most people die within the first year of diagnosis. The latest survival data for England and Wales (patients diagnosed during 2007) show that only one in ten people survives esophageal cancer for at least ten years. Individualized prognosis depends largely on stage. Those with cancer restricted entirely to the esophageal
mucosa A mucous membrane or mucosa is a membrane that lines various cavities in the body of an organism and covers the surface of internal organs. It consists of one or more layers of epithelial cells overlying a layer of loose connective tissue. It ...
have about an 80% 5YSR, but
submucosa The submucosa (or tela submucosa) is a thin layer of tissue in various organs of the gastrointestinal, respiratory, and genitourinary tracts. It is the layer of dense irregular connective tissue that supports the mucosa (mucous membrane) an ...
l involvement brings this down to less than 50%. Extension into the muscularis propria (muscle layer of the esophagus) suggests a 20% 5YSR, and extension to the structures adjacent to the esophagus predict a 7% 5YSR. Patients with distant metastases (who are not candidates for curative surgery) have a less than 3% 5YSR.


Epidemiology

Esophageal cancer is the eighth-most frequently-diagnosed cancer worldwide, and because of its poor prognosis, it is the sixth most-common cause of cancer-related deaths. It caused about 400,000 deaths in 2012, accounting for about 5% of all cancer deaths (about 456,000 new cases were diagnosed, representing about 3% of all cancers). ESCC (esophageal squamous-cell carcinoma) comprises 60–70% of all cases of esophageal cancer worldwide, while EAC (esophageal adenocarcinoma) accounts for a further 20–30% (melanomas, leiomyosarcomas, carcinoids and lymphomas are less common types). The incidence of the two main types of esophageal cancer varies greatly between different geographical areas. In general, ESCC is more common in the
developing world A developing country is a sovereign state with a less-developed industrial base and a lower Human Development Index (HDI) relative to developed countries. However, this definition is not universally agreed upon. There is also no clear agreeme ...
, and EAC is more common in the
developed world A developed country, or advanced country, is a sovereign state that has a high quality of life, developed economy, and advanced technological infrastructure relative to other less industrialized nations. Most commonly, the criteria for eval ...
. The worldwide
incidence rate In epidemiology Epidemiology is the study and analysis of the distribution (who, when, and where), patterns and Risk factor (epidemiology), determinants of health and disease conditions in a defined population, and application of this knowl ...
of ESCC in 2012 was 5.2 new cases per 100,000 person-years, with a male predominance (7.7 per 100,000 in men vs. 2.8 in women). It was the common type in 90% of the countries studied. ESCC is particularly frequent in the so-called "Asian esophageal cancer belt", an area that passes through
northern China Northern China () and Southern China () are two approximate regions that display certain differences in terms of their geography, demographics, economy, and culture. Extent The Qinling, Qinling–Daba Mountains serve as the transition zone ...
, southern
Russia Russia, or the Russian Federation, is a country spanning Eastern Europe and North Asia. It is the list of countries and dependencies by area, largest country in the world, and extends across Time in Russia, eleven time zones, sharing Borders ...
, north-eastern
Iran Iran, officially the Islamic Republic of Iran (IRI) and also known as Persia, is a country in West Asia. It borders Iraq to the west, Turkey, Azerbaijan, and Armenia to the northwest, the Caspian Sea to the north, Turkmenistan to the nort ...
, northern
Afghanistan Afghanistan, officially the Islamic Emirate of Afghanistan, is a landlocked country located at the crossroads of Central Asia and South Asia. It is bordered by Pakistan to the Durand Line, east and south, Iran to the Afghanistan–Iran borde ...
and eastern
Turkey Turkey, officially the Republic of Türkiye, is a country mainly located in Anatolia in West Asia, with a relatively small part called East Thrace in Southeast Europe. It borders the Black Sea to the north; Georgia (country), Georgia, Armen ...
. In 2012, about 80% of ESCC cases worldwide occurred in central and south-eastern Asia, and over half (53%) of all cases were in China. The countries with the highest estimated national incidence rates were (in Asia)
Mongolia Mongolia is a landlocked country in East Asia, bordered by Russia to the north and China to the south and southeast. It covers an area of , with a population of 3.5 million, making it the world's List of countries and dependencies by po ...
and
Turkmenistan Turkmenistan is a landlocked country in Central Asia bordered by Kazakhstan to the northwest, Uzbekistan to the north, east and northeast, Afghanistan to the southeast, Iran to the south and southwest and the Caspian Sea to the west. Ash ...
and (in Africa)
Malawi Malawi, officially the Republic of Malawi, is a landlocked country in Southeastern Africa. It is bordered by Zambia to the west, Tanzania to the north and northeast, and Mozambique to the east, south, and southwest. Malawi spans over and ...
,
Kenya Kenya, officially the Republic of Kenya, is a country located in East Africa. With an estimated population of more than 52.4 million as of mid-2024, Kenya is the 27th-most-populous country in the world and the 7th most populous in Africa. ...
and
Uganda Uganda, officially the Republic of Uganda, is a landlocked country in East Africa. It is bordered to the east by Kenya, to the north by South Sudan, to the west by the Democratic Republic of the Congo, to the south-west by Rwanda, and to the ...
. The problem of esophageal cancer has long been recognized in the eastern and southern parts of
Sub-Saharan Africa Sub-Saharan Africa is the area and regions of the continent of Africa that lie south of the Sahara. These include Central Africa, East Africa, Southern Africa, and West Africa. Geopolitically, in addition to the list of sovereign states and ...
, where ESCC appears to predominate. In Western countries, EAC has become the dominant form of the disease, following an increase in incidence over recent decades (in contrast to the incidence of ESCC, which has remained largely stable). In 2012, the global incidence rate for EAC was 0.7 per 100,000 with a strong male predominance (1.1 per 100,000 in men vs. 0.3 in women). Areas with particularly high incidence rates include northern and western Europe, North America and
Oceania Oceania ( , ) is a region, geographical region including Australasia, Melanesia, Micronesia, and Polynesia. Outside of the English-speaking world, Oceania is generally considered a continent, while Mainland Australia is regarded as its co ...
. The countries with highest recorded rates were the UK,
Netherlands , Terminology of the Low Countries, informally Holland, is a country in Northwestern Europe, with Caribbean Netherlands, overseas territories in the Caribbean. It is the largest of the four constituent countries of the Kingdom of the Nether ...
,
Ireland Ireland (, ; ; Ulster Scots dialect, Ulster-Scots: ) is an island in the North Atlantic Ocean, in Northwestern Europe. Geopolitically, the island is divided between the Republic of Ireland (officially Names of the Irish state, named Irelan ...
,
Iceland Iceland is a Nordic countries, Nordic island country between the Atlantic Ocean, North Atlantic and Arctic Oceans, on the Mid-Atlantic Ridge between North America and Europe. It is culturally and politically linked with Europe and is the regi ...
and
New Zealand New Zealand () is an island country in the southwestern Pacific Ocean. It consists of two main landmasses—the North Island () and the South Island ()—and List of islands of New Zealand, over 600 smaller islands. It is the List of isla ...
.


United States

In the United States, esophageal cancer is the seventh-leading cause of cancer-related deaths among males (making up 4% of the total). The
National Cancer Institute The National Cancer Institute (NCI) coordinates the United States National Cancer Program and is part of the National Institutes of Health (NIH), which is one of eleven agencies that are part of the U.S. Department of Health and Human Services. ...
estimated that there were about 18,000 new cases and more than 15,000 deaths from esophageal cancer in 2013; the
American Cancer Society The American Cancer Society (ACS) is a nationwide non-profit organization dedicated to eliminating cancer. The ACS publishes the journals ''Cancer'', '' CA: A Cancer Journal for Clinicians'' and '' Cancer Cytopathology''. History The society w ...
estimated that during 2014, about 18,170 new esophageal cancer cases would be diagnosed, resulting in 15,450 deaths. The squamous-cell carcinoma type is more common among
African American African Americans, also known as Black Americans and formerly also called Afro-Americans, are an Race and ethnicity in the United States, American racial and ethnic group that consists of Americans who have total or partial ancestry from an ...
males with a history of heavy smoking or alcohol use. Until the 1970s, squamous-cell carcinoma accounted for 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 contrast to squamous-cell carcinoma, esophageal adenocarcinoma is more common in
white American White Americans (sometimes also called Caucasian Americans) are Americans who identify as white people. In a more official sense, the United States Census Bureau, which collects demographic data on Americans, defines "white" as " person having ...
men (over the age of 60) than it is in African Americans. Multiple reports indicate esophageal adenocarcinoma incidence has increased during the past 20 years, especially in non-Hispanic white men. Esophageal adenocarcinoma age-adjusted incidence increased in
New Mexico New Mexico is a state in the Southwestern United States, Southwestern region of the United States. It is one of the Mountain States of the southern Rocky Mountains, sharing the Four Corners region with Utah, Colorado, and Arizona. It also ...
from 1973 to 2002. This increase was found in non-Hispanic whites and
Hispanics The term Hispanic () are people, cultures, or countries related to Spain, the Spanish language, or broadly. In some contexts, especially within the United States, "Hispanic" is used as an ethnic or meta-ethnic term. The term commonly appli ...
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 whites it has continued to increase. Between 1975 and 2004, incidence of the adenocarcinoma type increased among white American males by over 460% and among white American females by 335%.


United Kingdom

The incidence of esophageal adenocarcinoma has risen considerably in the UK in recent decades. Overall, esophageal cancer is the thirteenth most common cancer in the UK (around 8,300 people were diagnosed with the disease in 2011), and it is the sixth most common cause of cancer death (around 7,700 people died in 2012).


Society and culture


Notable cases

Humphrey Bogart Humphrey DeForest Bogart ( ; December 25, 1899 – January 14, 1957), nicknamed Bogie, was an American actor. His performances in classic Hollywood cinema made him an American cultural icon. In 1999, the American Film Institute selected Bogart ...
, actor, died of esophageal cancer in 1957, aged 57.
Billy Strayhorn William Thomas Strayhorn (November 29, 1915 – May 31, 1967) was an American jazz composer, pianist, lyricist, and arranger who collaborated with bandleader and composer Duke Ellington for nearly three decades. His compositions include "Take the ...
, American
jazz Jazz is a music genre that originated in the African-American communities of New Orleans, Louisiana, in the late 19th and early 20th centuries. Its roots are in blues, ragtime, European harmony, African rhythmic rituals, spirituals, h ...
composer, pianist,
lyricist A lyricist is a writer who writes lyrics (the spoken words), as opposed to a composer, who writes the song's music which may include but not limited to the melody, harmony, arrangement and accompaniment. Royalties A lyricist's income derives ...
, and
arranger In music, an arrangement is a musical adaptation of an existing composition. Differences from the original composition may include reharmonization, melodic paraphrasing, orchestration, or formal development. Arranging differs from orchestrat ...
, who collaborated with bandleader and composer
Duke Ellington Edward Kennedy "Duke" Ellington (April 29, 1899 – May 24, 1974) was an American Jazz piano, jazz pianist, composer, and leader of his eponymous Big band, jazz orchestra from 1924 through the rest of his life. Born and raised in Washington, D ...
, died of esophageal cancer in 1967 at age 51. Actor
John Thaw John Edward Thaw (3 January 1942 – 21 February 2002) was an English actor in television, stage and cinema, best known for his television roles starring as Detective Inspector Jack Regan in '' The Sweeney'' (1975—78) and as Detective Chief ...
died of esophageal cancer in 2002, at the age of 60.
Christopher Hitchens Christopher Eric Hitchens (13 April 1949 – 15 December 2011) was a British and American author and journalist. He was the author of Christopher Hitchens bibliography, 18 books on faith, religion, culture, politics, and literature. He was born ...
, author and journalist, died of esophageal cancer in 2011, aged 62.
Morrissey Steven Patrick Morrissey ( ; born 22 May 1959), known :wikt:mononym, mononymously as Morrissey, is an English singer and songwriter. He came to prominence as the frontman and lyricist of rock band the Smiths, who were active from 1982 to 198 ...
in October 2015 stated he has the disease and has described his experience when he first heard he had it. Mako Iwamatsu, voice actor for '' Avatar: The Last Airbender'' as General
Iroh Iroh (listed as Uncle in onscreen credits) is a fictional character in Nickelodeon's animated television series '' Avatar: The Last Airbender''. Created by Michael Dante DiMartino and Bryan Konietzko, the character was voiced by Mako in the fi ...
and '' Samurai Jack'' as Aku, died of esophageal cancer in 2006, aged 72. Robert Kardashian, attorney and businessman, died of esophageal cancer in 2003, aged 59. Traci Braxton, singer and reality TV star, died of esophageal cancer in 2022, aged 50. Andrew Bonar Law resigned as
Prime Minister of the United Kingdom The prime minister of the United Kingdom is the head of government of the United Kingdom. The prime minister Advice (constitutional law), advises the Monarchy of the United Kingdom, sovereign on the exercise of much of the Royal prerogative ...
in 1923 and died of throat cancer shortly after aged 65.
Ed Sullivan Edward Vincent Sullivan (September 28, 1901 – October 13, 1974) was an American television host, impresario, sports and entertainment reporter, and syndicated columnist for the ''New York Daily News'' and the Chicago Tribune New York News ...
, host of the prominent self-titled television program ''
The Ed Sullivan Show ''The Ed Sullivan Show'' is an American television variety show that ran on CBS from June 20, 1948, to March 28, 1971, and was hosted by New York City, New York entertainment columnist Ed Sullivan. It was replaced in September 1971 by the ''CB ...
'', died of esophageal cancer in 1974 at the age of 73. Lynn Yamada Davis, chef YouTube star, died of esophageal cancer in 2024, aged 67.


Research directions

The risk of esophageal squamous-cell carcinoma may be reduced in people using
aspirin Aspirin () is the genericized trademark for acetylsalicylic acid (ASA), a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and inflammation, and as an antithrombotic. Specific inflammatory conditions that aspirin is ...
or related
NSAID Non-steroidal anti-inflammatory drugs (NSAID) are members of a therapeutic drug class which reduces pain, decreases inflammation, decreases fever, and prevents blood clots. Side effects depend on the specific drug, its dose and duration of ...
s, but in the absence of
randomized controlled trial A randomized controlled trial (or randomized control trial; RCT) is a form of scientific experiment used to control factors not under direct experimental control. Examples of RCTs are clinical trials that compare the effects of drugs, surgical ...
s the current evidence is inconclusive. The genomics of esophageal adenocarcinoma is being studied using
cancer genome sequencing Cancer genome sequencing is the whole genome sequencing of a single, homogeneous or heterogeneous group of cancer cells. It is a biochemical laboratory method for the characterization and identification of the DNA or RNA sequences of cancer cell(s). ...
. Esophageal adenocarcinoma is characterized by complex tumor genomes with heterogeneity within the tumor micro-environment.


See also

* Esophagogastric junctional adenocarcinoma


References


External links


NCI esophageal cancer

Cancer.Net: Esophageal Cancer

Esophageal Cancer
Fro
Cancer Management: A Multidisciplinary Approach

Oesophageal Cancer at Cancer Research UK


{{DEFAULTSORT:Esophageal Cancer Gastrointestinal cancer Wikipedia medicine articles ready to translate