HOME

TheInfoList



OR:

Esophageal cancer is
cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
arising from the
esophagus The esophagus (American English) or oesophagus (British English; both ), non-technically known also as the food pipe or gullet, is an organ in vertebrates through which food passes, aided by peristaltic contractions, from the pharynx to t ...
—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 Lymphadenopathy or adenopathy is a disease of the lymph nodes, in which they are abnormal in size or consistency. Lymphadenopathy of an inflammatory type (the most common type) is lymphadenitis, producing swollen or enlarged lymph nodes. In ...
("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 Squamous-cell carcinomas (SCCs), also known as epidermoid carcinomas, comprise a number of different types of cancer that begin in squamous cells. These cells form on the surface of the skin, on the lining of hollow organs in the body, and on th ...
(often abbreviated to ESCC), which is more common in the developing world, 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, o ...
(EAC), which is more common in the developed world. A number of less common types also occur. Squamous-cell carcinoma arises from the
epithelial cells Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellu ...
that line the esophagus. Adenocarcinoma arises from glandular 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 lining the lower portion of the esophagus, from stratified squamous epithelium to simple columnar epithelium with interspersed goblet cells ...
). Causes of the squamous-cell type include tobacco, alcohol, very hot drinks, poor diet, and chewing
betel nut The betel (''Piper betle'') is a vine of the family Piperaceae, which includes pepper and kava. The betel plant is native to Southeast Asia. It is an evergreen, dioecious perennial, with glossy heart-shaped leaves and white catkins. Betel pla ...
. The most common causes of the adenocarcinoma type are smoking tobacco,
obesity Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it may negatively affect health. People are classified as obese when their body mass index (BMI)—a person's ...
, and
acid reflux Gastroesophageal reflux disease (GERD) or gastro-oesophageal reflux disease (GORD) is one of the upper gastrointestinal chronic diseases where stomach content persistently and regularly flows up into the esophagus, resulting in symptoms and/ ...
. The disease is diagnosed by
biopsy A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, or an interventional cardiologist. The process involves extraction of sample cells or tissues for examination to determine the presence or extent of a dise ...
done by an endoscope (a fiberoptic camera). Prevention includes stopping smoking and eating a healthy diet. 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 ''cheirourgikē'' (composed of χείρ, "hand", and ἔργον, "work"), via la, chirurgiae, meaning "hand work". is a medical specialty that uses operative manual and instrumental techniques on a person to investigate or treat a pa ...
alone with the hope of a
cure A cure is a substance or procedure that ends a medical condition, such as a medication, a surgical operation, a change in lifestyle or even a philosophical mindset that helps end a person's sufferings; or the state of being healed, or cured. The ...
. In most other cases,
chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemother ...
with or without
radiation therapy Radiation therapy or radiotherapy, often abbreviated RT, RTx, or XRT, is a therapy using ionizing radiation, generally provided as part of cancer treatment to control or kill malignant cells and normally delivered by a linear accelerator. Rad ...
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 (derived from the Latin root , or 'to cloak') is an interdisciplinary medical caregiving approach aimed at optimizing quality of life and mitigating suffering among people with serious, complex, and often terminal illnesses. Wit ...
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 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 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 is common.
Pain Pain is a distressing feeling often caused by intense or damaging stimuli. The International Association for the Study of Pain defines pain as "an unpleasant sensory and emotional experience associated with, or resembling that associated with, ...
behind the breastbone or in the region around the stomach often feels like
heartburn Heartburn, also known as pyrosis, cardialgia or acid indigestion, is a burning sensation in the central chest or upper central abdomen. Heartburn is usually due to regurgitation of gastric acid (gastric reflux) into the esophagus. It is the ...
. 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) 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 recurrent laryngeal nerves, right and ...
. 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. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of th ...
and
vomiting Vomiting (also known as emesis and throwing up) is the involuntary, 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, gastroenter ...
, regurgitation of food and coughing. There is also an increased risk of aspiration pneumonia due to food entering the airways through the abnormal connections ( fistulas) that may develop between the esophagus and the
trachea The trachea, 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 air- breathing animals with lungs. The trachea extends from t ...
(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 m ...
. Hypercalcemia (excess calcium in the blood) may occur. If the cancer has spread elsewhere, symptoms related to
metastatic disease Metastasis is a pathogenic agent's spread 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, the ...
may appear. Common sites of spread include nearby lymph nodes, the
liver The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it i ...
,
lungs The lungs are the primary organs of the respiratory system in humans and most other animals, including some snails and a small number of fish. In mammals and most other vertebrates, two lungs are located near the backbone on either si ...
and bone. Liver metastasis can cause jaundice and abdominal swelling ( ascites). Lung metastasis can cause, among other symptoms, impaired breathing due to excess fluid around the lungs ( pleural effusion), and dyspnea (the feelings often associated with impaired breathing).


Causes

The two main types (i.e.
squamous-cell carcinoma Squamous-cell carcinomas (SCCs), also known as epidermoid carcinomas, comprise a number of different types of cancer that begin in squamous cells. These cells form on the surface of the skin, on the lining of hollow organs in the body, and on th ...
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, o ...
) 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 u ...
s. Squamous-cell carcinoma is linked to lifestyle factors such as
smoking Smoking is a practice in which a substance is burned and the resulting smoke is typically breathed in to be tasted and absorbed into the bloodstream. Most commonly, the substance used is the dried leaves of the tobacco plant, which have b ...
and alcohol. Adenocarcinoma has been linked to effects of long-term
acid reflux Gastroesophageal reflux disease (GERD) or gastro-oesophageal reflux disease (GORD) is one of the upper gastrointestinal chronic diseases where stomach content persistently and regularly flows up into the esophagus, resulting in symptoms and/ ...
. 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) 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. The term ''synergy'' comes from the Attic Greek word συνεργία ' from ', , meaning "working together". History In Christia ...
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 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, a property of various corrosive substances ** Sodium hydroxide, sometimes called ''caustic soda'' ** Potassium hydroxide, sometimes called ''caustic potash'' ** Calcium oxide, sometimes called ''caust ...
substances. High levels of dietary exposure to nitrosamines (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, low socioeconomic status, and poor
oral hygiene Oral hygiene is the practice of keeping one's mouth clean and free of disease and other problems (e.g. bad breath) by regular brushing of the teeth (dental hygiene) and cleaning between the teeth. It is important that oral hygiene be carried ou ...
. Chewing
betel nut The betel (''Piper betle'') is a vine of the family Piperaceae, which includes pepper and kava. The betel plant is native to Southeast Asia. It is an evergreen, dioecious perennial, with glossy heart-shaped leaves and white catkins. Betel pla ...
(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 this type of esophageal cancer, which occurs about 7 to 10 times more frequently in men. This imbalance may be related to the characteristics and
interactions Interaction is action that occurs between two or more objects, with broad use in philosophy and the sciences. It may refer to: Science * Interaction hypothesis, a theory of second language acquisition * Interaction (statistics) * Interactions ...
of other known risk factors, including acid reflux and
obesity Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it may negatively affect health. People are classified as obese when their body mass index (BMI)—a person's ...
. The long-term erosive effects of acid reflux (an extremely common condition, also known as gastroesophageal reflux disease 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 lining the lower portion of the esophagus, from stratified squamous epithelium to simple columnar epithelium with interspersed goblet cells ...
, 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 Homeobox protein Hox-A13 is a protein that in humans is encoded by the ''HOXA13'' gene. Function In vertebrates, the genes encoding the class of transcription factors called homeobox genes are found in clusters named A, B, C, and D on four se ...
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. Bile acids are conjugated with taurine or glycine residues to give anions called bile salts. Primar ...
, including deoxycholic acid and chenodeoxycholic acid, appears to contribute to esophageal adenocarcinoma carcinogenesis by inducing oxidative stress and
DNA damage DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA d ...
.The risk of developing adenocarcinoma in the presence of Barrett's esophagus is unclear, and may in the past have been overestimated. Being obese or
overweight Being overweight or fat 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 m ...
both appear to be associated with increased risk. The association with obesity seems to 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 a condition when excessive visceral fat around the stomach and abdomen has built up to the extent that it is likely to have a negative impact on health. Abdominal obesity h ...
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'' 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 cancer that develops from the lining of the stomach. Most cases of stomach cancers are gastric carcinomas, which can be divided into a number of subtypes, including gastric adenocarcinomas. Lym ...
, 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, 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. 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, or nursing, is the process by which human breast milk is fed to a child. Breast milk may be from the breast, or may be expressed by hand or pumped and fed to the infant. The World Health Organization (WHO) recommends that bre ...
. 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 develops from tissues in the lip and oral cavity (mouth), larynx (throat), salivary glands, nose, sinuses or the skin of the face. The most common types of head and neck cancers occur in the lip, mouth, and larynx. Symptom ...
is associated with second primary tumors 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 substance, radionuclide, or radiation that promotes carcinogenesis (the formation of cancer). This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes. Several radioactive sub ...
ic exposure). * History of
radiation therapy Radiation therapy or radiotherapy, often abbreviated RT, RTx, or XRT, is a therapy using ionizing radiation, generally provided as part of cancer treatment to control or kill malignant cells and normally delivered by a linear accelerator. Rad ...
for other conditions in the chest is a risk factor for esophageal adenocarcinoma. * Corrosive injury to the esophagus by accidentally or intentionally swallowing
caustic Caustic most commonly refers to: * Causticity, a property of various corrosive substances ** Sodium hydroxide, sometimes called ''caustic soda'' ** Potassium hydroxide, sometimes called ''caustic potash'' ** Calcium oxide, sometimes called ''caust ...
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 (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 Plummer–Vinson syndrome is a rare disease characterized by difficulty swallowing, iron-deficiency anemia, glossitis, cheilosis and esophageal webs. Treatment with iron supplementation and mechanical widening of the esophagus generally provid ...
(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 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, 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 or barium meal, the diagnosis is best made with an examination using an endoscope. 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 A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, or an interventional cardiologist. The process involves extraction of sample cells or tissues for examination to determine the presence or extent of a disea ...
taken of suspicious lesions are then examined histologically for signs of malignancy. Additional testing is needed to assess how much the cancer has spread (see , below). Computed tomography (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 organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it i ...
and lymph nodes). The sensitivity of a CT scan is limited by its ability to detect masses (e.g. enlarged lymph nodes or involved organs) generally larger than 1 cm. Positron emission tomography 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 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 or photomicrograph is a photograph or digital image taken through a microscope or similar device to show a magnified image of an object. This is opposed to a macrograph or photomacrograph, an image which is also taken on a m ...
showing histopathological 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, mesoderm ...
s that arise from the
epithelium Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellul ...
, 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 develops from tissues in the lip and oral cavity (mouth), larynx (throat), salivary glands, nose, sinuses or the skin of the face. The most common types of head and neck cancers occur in the lip, mouth, and larynx. Symptom ...
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 Leiomyosarcoma is a malignant (cancerous) smooth muscle tumor. A benign tumor originating from the same tissue is termed leiomyoma. While leiomyosarcomas are not thought to arise from leiomyomas, some leiomyoma variants' classification is evolvi ...
,
malignant melanoma Melanoma, also redundantly known as malignant melanoma, is a type of skin cancer that develops from the pigment-producing cells known as melanocytes. Melanomas typically occur in the skin, but may rarely occur in the mouth, intestines, or eye ...
, rhabdomyosarcoma and
lymphoma Lymphoma is a group of blood and lymph tumors that develop from lymphocytes (a type of white blood cell). In current usage the name usually refers to just the cancerous versions rather than all such tumours. Signs and symptoms may include en ...
, among others.


Staging

Staging is based on the TNM staging system, which classifies the amount of tumor invasion (T), involvement of
lymph nodes 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 ...
(N), and distant
metastasis Metastasis is a pathogenic agent's spread 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, the ...
(M). The currently preferred classification is the 2010
AJCC staging system The TNM Classification of Malignant Tumors (TNM) is a globally recognised standard for classifying the extent of spread of cancer. It is a classification system of the anatomical extent of tumor cancers. It has gained wide international acceptance ...
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. T ...
, "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 (in British English fibre) 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 composition, and can be grouped generally by t ...
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 lining the lower portion of the esophagus, from stratified squamous epithelium to simple columnar epithelium with interspersed goblet cells ...
(a change in 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. Some areas of the world with high rates of squamous-carcinoma have screening programs.


Management

Treatment is best managed by a multidisciplinary team covering the various specialties involved. Adequate
nutrition Nutrition is the biochemical and physiological process by which an organism uses food to support its life. It provides organisms with nutrients, which can be metabolized to create energy and chemical structures. Failure to obtain sufficient ...
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 spread 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, the ...
: 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, often abbreviated RT, RTx, or XRT, is a therapy using ionizing radiation, generally provided as part of cancer treatment to control or kill malignant cells and normally delivered by a linear accelerator. Rad ...
or stenting 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 or lining of the esophagus may be removed by
endoscopic mucosal resection Endoscopic mucosal resection is a technique used to remove cancerous or other abnormal lesions found in the digestive tract. It is one method of performing a mucosectomy. For the esophagous Endoscopic mucosal resection has been advocated for ...
(EMR). Otherwise, curative surgery of early-stage lesions may entail removal of all or part of the esophagus ( esophagectomy), 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 As well as characteristics and location of the tumor, other factors include the patient's condition, and the type of operation the surgical team is most experienced with. 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 or part of the large intestine (colon) or jejunum. Reconnection of the stomach to a shortened esophagus is called an esophagogastric anastomosis. 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 Diaphragm may refer to: Anatomy * Thoracic diaphragm, a thin sheet of muscle between the thorax and the abdomen * Pelvic diaphragm or pelvic floor, a pelvic structure * Urogenital diaphragm or triangular ligament, a pelvic structure Other * Diap ...
) 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 ane ...
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 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 ...
, is removed ''en bloc''. If the person cannot swallow at all, an
esophageal stent An esophageal stent is a stent (tube) placed in the esophagus to keep a blocked area open so the patient can swallow soft food and liquids. They are effective in the treatment of conditions causing intrinsic esophageal obstruction or external ...
may be inserted to keep the esophagus open; stents 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 oesophagus, and down into the stomach. Orogastric intubation is a similar process involving the inserti ...
may be necessary to continue feeding while treatment for the tumor is given, and some patients require a gastrostomy (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.


Chemotherapy and radiotherapy

Chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemother ...
depends on the tumor type, but tends to be cisplatin-based (or
carboplatin Carboplatin, sold under the trade 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 used ...
or oxaliplatin) every three weeks with
fluorouracil Fluorouracil (5-FU), sold under the brand name Adrucil among others, is a cytotoxic chemotherapy medication used to treat cancer. By intravenous injection it is used for treatment of colorectal cancer, oesophageal cancer, stomach cancer, panc ...
(5-FU) either continuously or every three weeks. In more recent studies, addition of epirubicin was better than other comparable regimens in advanced nonresectable cancer. Chemotherapy may be given after surgery (adjuvant, i.e. to reduce risk of recurrence), before surgery (neoadjuvant) or if surgery is not possible; in this case, cisplatin and 5-FU are used. Ongoing trials compare various combinations of chemotherapy; the phase II/III REAL-2 trial – for example – compares four regimens containing epirubicin and either cisplatin or oxaliplatin, and either continuously infused fluorouracil or capecitabine.
Radiotherapy Radiation therapy or radiotherapy, often abbreviated RT, RTx, or XRT, is a therapy using ionizing radiation, generally provided as part of cancer treatment to control or kill malignant cells and normally delivered by a linear accelerator. Rad ...
is given before, during, or after chemotherapy or surgery, and sometimes on its own to control symptoms. In patients with localised 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 Endoscopic mucosal resection is a technique used to remove cancerous or other abnormal lesions found in the digestive tract. It is one method of performing a mucosectomy. For the esophagous Endoscopic mucosal resection has been advocated for ...
(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" is an acronym for "light amplification by stimulated emission of radiation". The ...
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, 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 (derived from the Latin root , or 'to cloak') is an interdisciplinary medical caregiving approach aimed at optimizing quality of life and mitigating suffering among people with serious, complex, and often terminal illnesses. Wit ...


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 (5YSR) in the United States is around 15%, with most people dying 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 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) and j ...
l involvement brings this down to less than 50%. Extension into the
muscularis propria The muscular layer (muscular coat, muscular fibers, muscularis propria, muscularis externa) is a region of muscle in many organs in the vertebrate body, adjacent to the submucosa. It is responsible for gut movement such as peristalsis. The Latin, ...
(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 death. 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, and EAC is more common in the developed world. The worldwide
incidence rate In epidemiology, incidence is a measure of the probability of occurrence of a given medical condition in a population within a specified period of time. Although sometimes loosely expressed simply as the number of new cases during some time p ...
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, southern
Russia Russia (, , ), or the Russian Federation, is a transcontinental country spanning Eastern Europe and Northern Asia. It is the largest country in the world, with its internationally recognised territory covering , and encompassing one-ei ...
, north-eastern
Iran Iran, officially the Islamic Republic of Iran, and also called Persia, is a country located in Western Asia. It is bordered by Iraq and Turkey to the west, by Azerbaijan and Armenia to the northwest, by the Caspian Sea and Turkmeni ...
, northern
Afghanistan Afghanistan, officially the Islamic Emirate of Afghanistan,; prs, امارت اسلامی افغانستان is a landlocked country located at the crossroads of Central Asia and South Asia. Referred to as the Heart of Asia, it is borde ...
and eastern
Turkey Turkey ( tr, Türkiye ), officially the Republic of Türkiye ( tr, Türkiye Cumhuriyeti, links=no ), is a transcontinental country located mainly on the Anatolian Peninsula in Western Asia, with a small portion on the Balkan Peninsula ...
. 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; Mongolian script: , , ; lit. "Mongol Nation" or "State of Mongolia" () is a landlocked country in East Asia, bordered by Russia to the north and China to the south. It covers an area of , with a population of just 3.3 million ...
and
Turkmenistan Turkmenistan ( or ; tk, Türkmenistan / Түркменистан, ) is a country located in Central Asia, bordered by Kazakhstan to the northwest, Uzbekistan to the north, east and northeast, Afghanistan to the southeast, Iran to the s ...
and (in Africa)
Malawi Malawi (; or aláwi Tumbuka: ''Malaŵi''), officially the Republic of Malawi, is a landlocked country in Southeastern Africa that was formerly known as Nyasaland. It is bordered by Zambia to the west, Tanzania to the north and northe ...
,
Kenya ) , national_anthem = " Ee Mungu Nguvu Yetu"() , image_map = , map_caption = , image_map2 = , capital = Nairobi , coordinates = , largest_city = Nairobi , ...
and
Uganda }), is a landlocked country in East Africa. The country 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 south by Tanzania. The ...
. The problem of esophageal cancer has long been recognized in the eastern and southern parts of
Sub-Saharan Africa Sub-Saharan Africa is, geographically, the area and regions of the continent of Africa that lies south of the Sahara. These include West Africa, East Africa, Central Africa, and Southern Africa. Geopolitically, in addition to the List of sov ...
, 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 geographical region that includes Australasia, Melanesia, Micronesia, and Polynesia. Spanning the Eastern and Western hemispheres, Oceania is estimated to have a land area of and a population of around 44.5 million ...
. The countries with highest recorded rates were the UK,
Netherlands ) , anthem = ( en, "William of Nassau") , image_map = , map_caption = , subdivision_type = Sovereign state , subdivision_name = Kingdom of the Netherlands , established_title = Before independence , established_date = Spanish Netherl ...
,
Ireland Ireland ( ; ga, Éire ; Ulster-Scots: ) is an island in the North Atlantic Ocean, in north-western Europe. It is separated from Great Britain to its east by the North Channel, the Irish Sea, and St George's Channel. Ireland is the s ...
,
Iceland Iceland ( is, Ísland; ) is a Nordic island country in the North Atlantic Ocean and in the Arctic Ocean. Iceland is the most sparsely populated country in Europe. Iceland's capital and largest city is Reykjavík, which (along with its ...
and
New Zealand New Zealand ( mi, Aotearoa ) is an island country in the southwestern Pacific Ocean. It consists of two main landmasses—the North Island () and the South Island ()—and over 700 smaller islands. It is the sixth-largest island coun ...
.


United States

In the United States, esophageal cancer is the seventh-leading cause of cancer death 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. T ...
estimated there were about 18,000 new cases and more than 15,000 deaths from esophageal cancer in 2013 (the American Cancer Society 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 referred to as Black Americans and Afro-Americans) are an ethnic group consisting of Americans with partial or total ancestry from sub-Saharan Africa. The term "African American" generally denotes descendants of ens ...
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 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 years, especially in non-Hispanic white men. Esophageal adenocarcinoma age-adjusted incidence increased in
New Mexico ) , population_demonym = New Mexican ( es, Neomexicano, Neomejicano, Nuevo Mexicano) , seat = Santa Fe, New Mexico, Santa Fe , LargestCity = Albuquerque, New Mexico, Albuquerque , LargestMetro = Albuquerque metropolitan area, Tiguex , Offi ...
from 1973 to 2002. This increase was found in non-Hispanic whites and
Hispanics The term ''Hispanic'' ( es, hispano) refers to people, cultures, or countries related to Spain, the Spanish language, or Hispanidad. The term commonly applies to countries with a cultural and historical link to Spain and to viceroyalties for ...
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 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 film and stage actor. His performances in Classical Hollywood cinema films made him an American cultural icon. In 1999, the American Film In ...
, actor, died of esophageal cancer in 1957, aged 57. Christopher Hitchens, author and journalist, died of esophageal cancer in 2011, aged 62.
Morrissey Steven Patrick Morrissey (; born 22 May 1959), known professionally 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 1987. Since th ...
in October 2015 stated he has the disease and describes his experience when he first heard he had it. Mako Iwamatsu, voice actor for Avatar: The Last Airbender as General
Iroh Uncle Iroh (), also referred to as General Iroh and credited simply as Uncle, is a fictional character in Nickelodeon's animated television series '' Avatar: The Last Airbender''. Created by Michael Dante DiMartino and Bryan Konietzko, the charac ...
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 Traci Renee Braxton (April 2, 1971 – March 12, 2022) was an American singer, reality television personality, and radio personality. Early life Braxton was born in Severn, Maryland as the third child of her parents. Her father, Michael Conra ...
, singer and reality TV star died of esophageal cancer in 2022, aged 50.


Research directions

The risk of esophageal squamous-cell carcinoma may be reduced in people using
aspirin Aspirin, also known as acetylsalicylic acid (ASA), is a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and/or inflammation, and as an antithrombotic. Specific inflammatory conditions which aspirin is used to treat inc ...
or related NSAIDs, 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 t ...
s the current evidence is inconclusive.


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