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Stomach cancer, also known as gastric cancer, is a
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 ...
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. Lymphomas and mesenchymal tumors may also develop in the stomach. Early symptoms may include
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 ...
, upper abdominal pain,
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 loss of appetite. Later signs and symptoms may include weight loss, yellowing of the skin and whites of the eyes,
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 ...
, difficulty swallowing, and blood in the stool, among others. The cancer may spread from the stomach to other parts of the body, particularly 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 ...
,
bone A bone is a rigid organ that constitutes part of the skeleton in most vertebrate animals. Bones protect the various other organs of the body, produce red and white blood cells, store minerals, provide structure and support for the body, ...
s, lining of the abdomen, and lymph nodes. The most common cause is infection by the
bacterium Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were am ...
'' Helicobacter pylori'', which accounts for more than 60% of cases. Certain types of ''H. pylori'' have greater risks than others. Smoking, dietary factors such as pickled vegetables 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 ...
are other risk factors. About 10% of cases run in families, and between 1% and 3% of cases are due to
genetic syndromes A syndrome is a set of medical signs and symptoms which are correlated with each other and often associated with a particular disease or disorder. The word derives from the Greek σύνδρομον, meaning "concurrence". When a syndrome is paired ...
inherited from a person's parents such as
hereditary diffuse gastric cancer Hereditary diffuse gastric cancer (HDGC) is an inherited genetic syndrome most often caused by an inactivating mutation in the E-cadherin gene (CDH1) located on chromosome 16. Individuals who inherit an inactive copy of the CDH1 gene are at signi ...
. Most of the time, stomach cancer develops in stages over years. Diagnosis is usually 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 during
endoscopy An endoscopy is a procedure used in medicine to look inside the body. The endoscopy procedure uses an endoscope to examine the interior of a hollow organ or cavity of the body. Unlike many other medical imaging techniques, endoscopes are inse ...
. This is followed by
medical imaging Medical imaging is the technique and process of imaging the interior of a body for clinical analysis and medical intervention, as well as visual representation of the function of some organs or tissues (physiology). Medical imaging seeks to re ...
to determine if the disease has spread to other parts of the body.
Japan Japan ( ja, 日本, or , and formally , ''Nihonkoku'') is an island country in East Asia. It is situated in the northwest Pacific Ocean, and is bordered on the west by the Sea of Japan, while extending from the Sea of Okhotsk in the n ...
and
South Korea South Korea, officially the Republic of Korea (ROK), is a country in East Asia, constituting the southern part of the Korea, Korean Peninsula and sharing a Korean Demilitarized Zone, land border with North Korea. Its western border is formed ...
, two countries that have high rates of the disease, screen for stomach cancer. A Mediterranean diet lowers the risk of stomach cancer, as does the stopping of smoking. Tentative evidence indicates that treating ''H. pylori'' decreases the future risk. If stomach cancer is treated early, it can be cured. Treatments may include some combination of surgery,
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 ...
,
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 ...
, and targeted therapy. For certain subtypes of gastric cancer,
cancer immunotherapy Cancer immunotherapy (sometimes called immuno-oncology) is the stimulation of the immune system to treat cancer, improving on the immune system's natural ability to fight the disease. It is an application of the fundamental research of cancer ...
is an option as well. If treated late,
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 ...
may be advised. Some types of lymphoma can be cured by eliminating ''H. pylori''. Outcomes are often poor, with a less than 10% five-year survival rate in the Western world for advanced cases. This is largely because most people with the condition present with advanced disease. In the United States, five-year survival is 31.5%, while in South Korea it is over 65% and Japan over 70%, partly due to screening efforts. Globally, stomach cancer is the fifth-leading type of cancer and the third-leading cause of death from cancer, making up 7% of cases and 9% of deaths. In 2018, it newly occurred in 1.03 million people and caused 783,000 deaths. Before the 1930s, in much of the world, including most Western developed countries, it was the most common cause of death from cancer. Rates of death have been decreasing in many areas of the world since then. This is believed to be due to the eating of less salted and pickled foods as a result of the development of refrigeration as a method of storing food. Stomach cancer occurs most commonly in
East Asia East Asia is the eastern region of Asia, which is defined in both geographical and ethno-cultural terms. The modern states of East Asia include China, Japan, Mongolia, North Korea, South Korea, and Taiwan. China, North Korea, South Korea ...
and
Eastern Europe Eastern Europe is a subregion of the European continent. As a largely ambiguous term, it has a wide range of geopolitical, geographical, ethnic, cultural, and socio-economic connotations. The vast majority of the region is covered by Russia, whi ...
. It occurs twice as often in males as in females.


Signs and symptoms

Stomach cancer is often either asymptomatic (producing no noticeable symptoms) or it may cause only
nonspecific symptoms Signs and symptoms are the observed or detectable signs, and experienced symptoms of an illness, injury, or condition. A sign for example may be a higher or lower temperature than normal, raised or lowered blood pressure or an abnormality showi ...
(which may also be present in other related or unrelated disorders) in its early stages. By the time symptoms are recognized, the cancer has often reached an advanced stage (see below) and may have metastasized (spread to other, perhaps distant, parts of the body), which is one of the main reasons for its relatively poor prognosis. Stomach cancer can cause the following signs and symptoms: Unexplained nausea, vomiting, diarrhoea and constipation. Patients also can experience unexplained weight loss. Early cancers may be associated with
indigestion Indigestion, also known as dyspepsia or upset stomach, is a condition of impaired digestion. Symptoms may include upper abdominal fullness, heartburn, nausea, belching, or upper abdominal pain. People may also experience feeling full earlier t ...
or a burning sensation (
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 ...
). However, fewer than one in every 50 people referred for endoscopy due to indigestion has cancer. Abdominal discomfort and loss of appetite, especially for meat, can occur. Gastric cancers that have enlarged and invaded normal tissue can cause
weakness Weakness is a symptom of a number of different conditions. The causes are many and can be divided into conditions that have true or perceived muscle weakness. True muscle weakness is a primary symptom of a variety of skeletal muscle diseases, i ...
, fatigue, bloating of the stomach after meals,
abdominal pain Abdominal pain, also known as a stomach ache, is a symptom associated with both non-serious and serious medical issues. Common causes of pain in the abdomen include gastroenteritis and irritable bowel syndrome. About 15% of people have a m ...
in the upper abdomen,
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 occasional
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 ...
. Further enlargement may cause weight loss or bleeding with vomiting blood or having blood in the stool, the latter apparent as black discolouration (
melena Melena or melaena refers to the dark black, tarry feces that are associated with upper gastrointestinal bleeding. The black color and characteristic strong odor are caused by hemoglobin in the blood being altered by digestive enzymes and intest ...
) and sometimes leading to
anemia Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, t ...
.
Dysphagia Dysphagia is difficulty in swallowing. Although classified under "symptoms and signs" in ICD-10, in some contexts it is classified as a condition in its own right. It may be a sensation that suggests difficulty in the passage of solids or liq ...
suggests a tumour in the
cardia The stomach is a muscular, hollow organ in the gastrointestinal tract of humans and many other animals, including several invertebrates. The stomach has a dilated structure and functions as a vital organ in the digestive system. The stomach is ...
or extension of the gastric tumour into 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 ...
. These can be symptoms of other problems such as a stomach virus, gastric ulcer, or tropical sprue.


Risk factors

Gastric cancer can occur as a result of many factors. It occurs twice as commonly in males as females.
Estrogen Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal ac ...
may protect women against the development of this form of cancer.


Infections

'' Helicobacter pylori'' infection is an essential risk factor in 65–80% of gastric cancers, but only 2% of people with ''H. pylori'' infections develop stomach cancer. The mechanism by which ''H. pylori'' induces stomach cancer potentially involves chronic inflammation, or the action of ''H. pylori'' virulence factors such as CagA. It was estimated that
Epstein–Barr virus The Epstein–Barr virus (EBV), formally called ''Human gammaherpesvirus 4'', is one of the nine known human herpesvirus types in the herpes family, and is one of the most common viruses in humans. EBV is a double-stranded DNA virus. It is ...
is responsible for 84,000 cases per year.
AIDS Human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS) is a spectrum of conditions caused by infection with the human immunodeficiency virus (HIV), a retrovirus. Following initial infection an individual ma ...
is also associated with elevated risk.


Smoking

Smoking increases the risk of developing gastric cancer significantly, from 40% increased risk for current smokers to 82% increase for heavy smokers. Gastric cancers due to smoking mostly occur in the upper part of the stomach near the esophagus.


Alcohol

Some studies show increased risk with alcohol consumption as well.


Diet

Dietary factors are not proven causes, and the association between stomach cancer and various foods and beverages is weak. Some foods including smoked foods, salt and salt-rich foods, red meat,
processed meat Processed meat is considered to be any meat which has been modified in order to either improve its taste or to extend its shelf life. Methods of meat processing include salting, curing, fermentation, smoking, and/or the addition of chemical pr ...
, pickled vegetables, and
bracken Bracken (''Pteridium'') is a genus of large, coarse ferns in the family (biology), family Dennstaedtiaceae. Ferns (Pteridophyta) are vascular plants that have alternating generations, large plants that produce spores and small plants that produ ...
s are associated with a higher risk of stomach cancer. Nitrates and nitrites in cured meats can be converted by certain bacteria, including ''H. pylori'', into compounds that have been found to cause stomach cancer in animals. Fresh fruit and vegetable intake, citrus fruit intake, and
antioxidant Antioxidants are compounds that inhibit oxidation, a chemical reaction that can produce free radicals. This can lead to polymerization and other chain reactions. They are frequently added to industrial products, such as fuels and lubrica ...
intake are associated with a lower risk of stomach cancer. A Mediterranean diet is associated with lower rates of stomach cancer, as is regular
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 ...
use. Obesity is a physical risk factor that has been found to increase the risk of gastric adenocarcinoma by contributing to the development of gastroesophageal reflux disease (GERD). The exact mechanism by which obesity causes GERD is not completely known. Studies hypothesize that increased dietary fat leading to increased pressure on the stomach and the lower esophageal sphincter, due to excess adipose tissue, could play a role, yet no statistically significant data have been collected. However, the risk of gastric cardia adenocarcinoma, with GERD present, has been found to increase more than 2 times for an obese person. There is a correlation between iodine deficiency and gastric cancer.


Genetics

About 10% of cases run in families, and between 1 and 3% of cases are due to genetic syndromes inherited from a person's parents such as
hereditary diffuse gastric cancer Hereditary diffuse gastric cancer (HDGC) is an inherited genetic syndrome most often caused by an inactivating mutation in the E-cadherin gene (CDH1) located on chromosome 16. Individuals who inherit an inactive copy of the CDH1 gene are at signi ...
. A genetic risk factor for gastric cancer is a genetic defect of the ''CDH1'' gene known as
hereditary diffuse gastric cancer Hereditary diffuse gastric cancer (HDGC) is an inherited genetic syndrome most often caused by an inactivating mutation in the E-cadherin gene (CDH1) located on chromosome 16. Individuals who inherit an inactive copy of the CDH1 gene are at signi ...
(HDGC). The ''CDH1'' gene, which codes for E-cadherin, lies on the 16th chromosome. When the gene experiences a particular mutation, gastric cancer develops through a mechanism that is not fully understood. This mutation is considered autosomal dominant, meaning that half of a carrier's children will likely experience the same mutation. Diagnosis of hereditary diffuse gastric cancer usually takes place when at least two cases involving a family member, such as a parent or grandparent, are diagnosed, with at least one diagnosed before the age of 50. The diagnosis can also be made if at least three cases occur in the family, in which case age is not considered. The International Cancer Genome Consortium is leading efforts to identify
genomic Genomics is an interdisciplinary field of biology focusing on the structure, function, evolution, mapping, and editing of genomes. A genome is an organism's complete set of DNA, including all of its genes as well as its hierarchical, three-dim ...
changes involved in stomach cancer. A very small percentage of diffuse-type gastric cancers (see Histopathology below) arise from an inherited abnormal '' CDH1''
gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
. Genetic testing and treatment options are available for families at risk.


Other

Other risk factors include
diabetes Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ...
,
pernicious anemia Pernicious anemia is a type of vitamin B12 deficiency anemia, a disease in which not enough red blood cells are produced due to the malabsorption of vitamin B12. Malabsorption in pernicious anemia results from the lack or loss of intrinsic ...
, chronic atrophic gastritis, Menetrier's disease (hyperplastic, hypersecretory gastropathy), and intestinal metaplasia. In addition, Foxp3 polymorphism (rs3761548) might contribute to
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 ...
development through influencing Treg cell activity.


Diagnosis

To find the cause of symptoms, the doctor asks about the patient's medical history, does a physical examination, and may order laboratory studies. The patient may also have one or all of these exams: * Gastroscopic exam is the diagnostic method of choice. This involves insertion of a fibre optic camera into the stomach to visualise it. *
Upper GI series 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 barium ...
(may be called barium roentgenogram) * Computed tomography or CT scanning of the abdomen may reveal gastric cancer. It is more useful to determine invasion into adjacent tissues or the presence of spread to local lymph nodes. Wall thickening of more than 1 cm that is focal, eccentric, and enhancing favours malignancy. In 2013, Chinese and Israeli scientists reported a successful pilot study of a
breathalyzer A breathalyzer or breathalyser (a portmanteau of ''breath'' and ''analyzer/analyser'') is a device for estimating blood alcohol content (BAC), or to detect viruses or diseases from a breath sample. The name is a genericized trademark of the Br ...
-style breath test intended to diagnose stomach cancer by analyzing exhaled chemicals without the need for an intrusive
endoscopy An endoscopy is a procedure used in medicine to look inside the body. The endoscopy procedure uses an endoscope to examine the interior of a hollow organ or cavity of the body. Unlike many other medical imaging techniques, endoscopes are inse ...
. A larger-scale
clinical trial Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, diet ...
of this technology was completed in 2014. Abnormal tissue seen in a gastroscope examination is biopsied by the
surgeon In modern medicine, a surgeon is a medical professional who performs surgery. Although there are different traditions in different times and places, a modern surgeon usually is also a licensed physician or received the same medical training as ...
or gastroenterologist. This tissue is then sent to a
pathologist Pathology is the study of the causes and effects of disease or injury. The word ''pathology'' also refers to the study of disease in general, incorporating a wide range of biology research fields and medical practices. However, when used in th ...
for histological examination under a microscope to check for the presence of cancerous cells. A biopsy, with subsequent histological analysis, is the only sure way to confirm the presence of cancer cells. Various gastroscopic modalities have been developed to increase yield of detected mucosa with a dye that accentuates the cell structure and can identify areas of dysplasia. Endocytoscopy involves ultra-high magnification to visualise cellular structure to better determine areas of dysplasia. Other gastroscopic modalities such as
optical coherence tomography Optical coherence tomography (OCT) is an imaging technique that uses low-coherence light to capture micrometer-resolution, two- and three-dimensional images from within optical scattering media (e.g., biological tissue). It is used for medica ...
are being tested investigationally for similar applications. A number of cutaneous conditions are associated with gastric cancer. A condition of darkened hyperplasia of the skin, frequently of the axilla and groin, known as acanthosis nigricans, is associated with intra-abdominal cancers such as gastric cancer. Other cutaneous manifestations of gastric cancer include "tripe palms" (a similar darkening hyperplasia of the skin of the palms) and the Leser-Trelat sign, which is the rapid development of skin lesions known as seborrheic keratoses. Various blood tests may be done, including a
complete blood count A complete blood count (CBC), also known as a full blood count (FBC), is a set of medical laboratory tests that provide information about the cells in a person's blood. The CBC indicates the counts of white blood cells, red blood cells and ...
to check for anaemia, and a fecal occult blood test to check for blood in the stool.


Histopathology

* ''Gastric
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 ...
'' is a malignant epithelial tumour, originating from glandular epithelium of the gastric mucosa. Stomach cancers are about 90% adenocarcinomas. Histologically, there are two major types of gastric adenocarcinoma ( Lauren classification): intestinal type or diffuse type. Adenocarcinomas tend to aggressively invade the gastric wall, infiltrating the
muscularis mucosae The lamina muscularis mucosae (or muscularis mucosae) is a thin layer ( lamina) of muscle of the gastrointestinal tract, located outside the lamina propria, and separating it from the submucosa. It is present in a continuous fashion from the e ...
, the
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 ...
and then 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, ...
. Intestinal type adenocarcinoma tumour cells describe irregular tubular structures, harbouring pluristratification, multiple lumens, reduced stroma ("back to back" aspect). Often, it associates intestinal metaplasia in neighbouring mucosa. Depending on glandular architecture, cellular pleomorphism and mucosecretion, adenocarcinoma may present 3 degrees of differentiation: well, moderate and poorly differentiated. Diffuse type adenocarcinoma (mucinous, colloid, linitis plastica or leather-bottle stomach) tumour cells are discohesive and secrete mucus, which is delivered in the interstitium, producing large pools of mucus/colloid (optically "empty" spaces). It is poorly differentiated. In signet-ring cell carcinomas, the mucus remains inside the tumour cell and pushes the nucleus to the periphery, giving rise to signet-ring cells. * Around 5% of gastric cancers are lymphomas. These may include extranodal marginal zone B-cell lymphomas (MALT type) and to a lesser extent
diffuse large B-cell lymphoma Diffuse large B-cell lymphoma (DLBCL) is a cancer of B cells, a type of lymphocyte that is responsible for producing antibodies. It is the most common form of non-Hodgkin lymphoma among adults, with an annual incidence of 7–8 cases per 100,00 ...
s. MALT type make up about half of stomach lymphomas. * Carcinoid and stromal tumors may occur. File:Adenocarcinoma low differentiated (stomach) H&E magn 400x.jpg, Poor to moderately differentiated adenocarcinoma of the stomach.
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 ...
. File:Gastric signet ring cell carcinoma histopatholgy (1).jpg, Gastric signet ring cell carcinoma.
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 ...
. File:Gastric adenocarcinoma.jpg, Adenocarcinoma of the stomach and intestinal metaplasia.
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 ...
.


Staging

If cancer cells are found in the tissue sample, the next step is to stage, or find out the extent of the disease. Various tests determine whether the cancer has spread, and if so, what parts of the body are affected. Because stomach cancer can spread to the liver, pancreas, and other organs near the stomach, as well as to the lungs, the doctor may order a CT scan, a
PET scan 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 flo ...
, an endoscopic ultrasound exam, or other tests to check these areas. Blood tests for tumor markers, such as
carcinoembryonic antigen Carcinoembryonic antigen (CEA) describes a set of highly related glycoproteins involved in cell adhesion. CEA is normally produced in gastrointestinal tissue during fetal development, but the production stops before birth. Consequently, CEA is u ...
and carbohydrate antigen may be ordered, as their levels correlate to extent of metastasis, especially to the liver, and the cure rate. Staging may not be complete until after surgery. The surgeon removes nearby lymph nodes and possibly samples of tissue from other areas in the abdomen for examination by a pathologist. The clinical stages of stomach cancer are: * Stage 0 – Limited to the inner lining of the stomach, it is treatable by endoscopic mucosal resection when found very early (in routine screenings), or otherwise by
gastrectomy A gastrectomy is a partial or total surgical removal of the stomach. Indications Gastrectomies are performed to treat stomach cancer and perforations of the stomach wall. In severe duodenal ulcers it may be necessary to remove the lower porti ...
and lymphadenectomy without need for chemotherapy or radiation. * Stage I – Penetration to the second or third layers of the stomach (stage 1A) or to the second layer and nearby
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 ...
(stage 1B): Stage 1A is treated by surgery, including removal of the omentum. Stage 1B may be treated with chemotherapy (
5-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 ...
) and radiation therapy. * Stage II – Penetration to the second layer and more distant lymph nodes, or the third layer and only nearby lymph nodes, or all four layers but not the lymph nodes, it is treated as for stage I, sometimes with additional
neoadjuvant chemotherapy Neoadjuvant therapy is the administration of therapeutic agents before a main treatment. One example is neoadjuvant hormone therapy prior to radical radiotherapy for adenocarcinoma of the prostate. Neoadjuvant therapy aims to reduce the size or ...
. * Stage III – Penetration to the third layer and more distant lymph nodes, or penetration to the fourth layer and either nearby tissues or nearby or more distant lymph nodes, it is treated as for stage II; a cure is still possible in some cases. * Stage IV – Cancer has spread to nearby tissues and more distant lymph nodes, or has metastasized to other organs. A cure is very rarely possible at this stage. Some other techniques to prolong life or improve symptoms are used, including laser treatment, surgery, and/or stents to keep the digestive tract open, and chemotherapy by drugs such as 5-fluorouracil, cisplatin, epirubicin, etoposide, docetaxel, oxaliplatin, capecitabine, or
irinotecan Irinotecan, sold under the brand name Camptosar among others, is a medication used to treat colon cancer, and small cell lung cancer. For colon cancer it is used either alone or with fluorouracil. For small cell lung cancer it is used with cispl ...
. The TNM staging system is also used. In a study of open-access endoscopy in
Scotland Scotland (, ) is a country that is part of the United Kingdom. Covering the northern third of the island of Great Britain, mainland Scotland has a border with England to the southeast and is otherwise surrounded by the Atlantic Ocean to ...
, patients were diagnosed 7% in stage I, 17% in stage II, and 28% in stage III. A Minnesota population was diagnosed 10% in stage I, 13% in stage II, and 18% in stage III. However, in a high-risk population in the Valdivia Province of southern
Chile Chile, officially the Republic of Chile, is a country in the western part of South America. It is the southernmost country in the world, and the closest to Antarctica, occupying a long and narrow strip of land between the Andes to the eas ...
, only 5% of patients were diagnosed in the first two stages and 10% in stage III.


Prevention

Getting rid of ''H. pylori'' in those who are infected decreases the risk of stomach cancer. A 2014 meta-analysis of observational studies found that a diet high in
fruit In botany, a fruit is the seed-bearing structure in flowering plants that is formed from the ovary after flowering. Fruits are the means by which flowering plants (also known as angiosperms) disseminate their seeds. Edible fruits in partic ...
s, mushrooms,
garlic Garlic (''Allium sativum'') is a species of bulbous flowering plant in the genus '' Allium''. Its close relatives include the onion, shallot, leek, chive, Welsh onion and Chinese onion. It is native to South Asia, Central Asia and northeas ...
,
soybean The soybean, soy bean, or soya bean (''Glycine max'') is a species of legume native to East Asia, widely grown for its edible bean, which has numerous uses. Traditional unfermented food uses of soybeans include soy milk, from which tofu ...
s, and green onions was associated with a lower risk of stomach cancer in the Korean population. Low doses of
vitamin A vitamin is an organic molecule (or a set of molecules closely related chemically, i.e. vitamers) that is an essential micronutrient that an organism needs in small quantities for the proper functioning of its metabolism. Essential nutrie ...
s, especially from a healthy diet, decrease the risk of stomach cancer. A previous review of
antioxidant Antioxidants are compounds that inhibit oxidation, a chemical reaction that can produce free radicals. This can lead to polymerization and other chain reactions. They are frequently added to industrial products, such as fuels and lubrica ...
supplementation did not find supporting evidence and possibly worse outcomes. Modern technology is used to promote early diagnosis, e.g. based on serum markers.


Management

Cancer of the stomach is difficult to cure unless it is found at an early stage (before it has begun to spread). Unfortunately, because early stomach cancer causes few symptoms, the disease is usually advanced when the diagnosis is made. Treatment for stomach cancer may include surgery,
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 ...
, or
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 ...
. New treatment approaches such as immunotherapy or
gene therapy Gene therapy is a Medicine, medical field which focuses on the genetic modification of cells to produce a therapeutic effect or the treatment of disease by repairing or reconstructing defective genetic material. The first attempt at modifying ...
and improved ways of using current methods are being studied in clinical trials.


Surgery

Surgery remains the only curative therapy for stomach cancer. Of the different surgical techniques,
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) is a treatment for early gastric cancer (tumor only involves the mucosa) that was pioneered in Japan and is available in the United States at some centers. In EMR, the tumor, together with the inner lining of stomach (mucosa), is removed from the wall of the stomach using an electrical wire loop through the endoscope. The advantage is that it is a much smaller operation than removing the stomach. Endoscopic submucosal dissection is a similar technique pioneered in Japan, used to resect a large area of mucosa in one piece. If the pathologic examination of the resected specimen shows incomplete resection or deep invasion by tumor, the patient would need a formal stomach resection. A 2016
Cochrane review Cochrane (previously known as the Cochrane Collaboration) is a British international charitable organisation formed to organise medical research findings to facilitate evidence-based choices about health interventions involving health professi ...
found low-quality evidence of no difference in short-term mortality between laparoscopic and open gastrectomy (removal of stomach), and that benefits or harms of laparoscopic gastrectomy cannot be ruled out. Post-operatively, up to 70% of people undergoing total gastrectomy develop complications such as dumping syndrome and reflux esophagitis. Construction of a "pouch", which serves as a "stomach substitute", reduced the incidence of dumping syndrome and reflux esophagitis by 73% and 63% respectively, and led to improvements in quality-of-life, nutritional outcomes, and body mass index. Those with metastatic disease at the time of presentation may receive palliative surgery, and while it remains controversial, due to the possibility of complications from the surgery itself and because it may delay chemotherapy, the data so far are mostly positive, with improved survival rates being seen in those treated with this approach.


Chemotherapy

The use of chemotherapy to treat stomach cancer has no firmly established standard of care. Unfortunately, stomach cancer has not been particularly sensitive to these drugs, and chemotherapy, if used, has usually served to palliatively reduce the size of the tumor, relieve symptoms of the disease, and increase survival time. Some drugs used in stomach cancer treatment have included: fluorouracil or its analog capecitabine, BCNU (
carmustine Carmustine, sold under the brand name BiCNU among others, is a medication used mainly for chemotherapy. It is a nitrogen mustard β-chloro- nitrosourea compound used as an alkylating agent. Description Carmustine is an orange-yellow solid medic ...
), methyl-CCNU (
semustine Semustine (1- (2-Chloroethyl)-3-(trans-4-methylcyclohexyl)- 1-nitrosourea, MeCCNU) is an alkylating nitrosourea compound used in chemotherapy treatment of various types of tumours. Due to its lipophilic property, semustine can cross the blood-bra ...
) and doxorubicin (Adriamycin), as well as mitomycin C, and more recently cisplatin and
taxotere Docetaxel (DTX or DXL), sold under the brand name Taxotere among others, is a chemotherapy medication used to treat a number of types of cancer. This includes breast cancer, head and neck cancer, stomach cancer, prostate cancer and non-small-cel ...
, often using drugs in various combinations. The relative benefits of these different drugs, alone and in combination, are unclear. Clinical researchers are exploring the benefits of giving chemotherapy before surgery to shrink the tumor, or as adjuvant therapy after surgery to destroy remaining cancer cells.


Targeted therapy

Recently, treatment with human epidermal growth factor receptor 2 (''HER2'') inhibitor,
trastuzumab Trastuzumab, sold under the brand name Herceptin among others, is a monoclonal antibody used to treat breast cancer and stomach cancer. It is specifically used for cancer that is HER2 receptor positive. It may be used by itself or together wi ...
, has been demonstrated to increase overall survival in inoperable locally advanced or metastatic gastric carcinoma over-expressing the '' HER2/neu'' gene. In particular, '' HER2'' is overexpressed in 13–22% of patients with gastric cancer. Of note, ''HER2'' overexpression in gastric neoplasia is heterogeneous and comprises a minority of tumor cells (less than 10% of gastric cancers overexpress ''HER2'' in more than 5% of tumor cells). Hence, this heterogeneous expression should be taken into account for ''HER2'' testing, particularly in small samples such as biopsies, requiring the evaluation of more than one bioptic sample.


Radiation

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 ...
(also called radiotherapy) may be used to treat stomach cancer, often as an adjuvant to chemotherapy and/or surgery.


Lymphoma

MALT lymphomas can often be fully treated by treating an underlying ''H. pylori'' infection. This results in remission in about 80% of cases.


Prognosis

The prognosis of stomach cancer is generally poor, because the tumor has often metastasized by the time of discovery, and most people with the condition are elderly (median age is between 70 and 75 years) at presentation. The average life expectancy after being diagnosed is around 24 months, and the five-year survival rate for stomach cancer is less than 10%. Almost 300 genes are related to outcomes in stomach cancer, with both unfavorable genes where high expression is related to poor survival and favorable genes where high expression is associated with longer survival times. Examples of poor prognosis genes include
ITGAV Integrin alpha-V is a protein that in humans is encoded by the ''ITGAV'' gene. Function ITGAV encodes integrin alpha chain V. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain. Alpha V undergoes ...
,
DUSP1 Dual specificity protein phosphatase 1 is an enzyme that in humans is encoded by the ''DUSP1'' gene. Function The expression of DUSP1 gene is induced in human skin fibroblasts by oxidative/heat stress and growth factors. It specifies a protei ...
and
P2RX7 P2X purinoceptor 7 is a protein that in humans is encoded by the ''P2RX7'' gene. The product of this gene belongs to the family of purinoceptors for ATP. Multiple alternatively spliced variants which would encode different isoforms have been id ...
.


Epidemiology

Worldwide, stomach cancer is the fifth most-common cancer with 952,000 cases diagnosed in 2012. It is more common both in men and in developing countries. In 2012, it represented 8.5% of cancer cases in men, making it the fourth-most common cancer in men. Also in 2012, the number of deaths was 700,000, having decreased slightly from 774,000 in 1990, making it the third-leading cause of cancer-related death (after
lung cancer Lung cancer, also known as lung carcinoma (since about 98–99% of all lung cancers are carcinomas), is a malignant lung tumor characterized by uncontrolled cell growth in tissues of the lung. Lung carcinomas derive from transformed, mali ...
and
liver cancer Liver cancer (also known as hepatic cancer, primary hepatic cancer, or primary hepatic malignancy) is cancer that starts in the liver. Liver cancer can be primary (starts in liver) or secondary (meaning cancer which has spread from elsewhere to th ...
). Less than 5% of stomach cancers occur in people under 40 years of age, with 81.1% of that 5% in the age-group of 30 to 39 and 18.9% in the age-group of 20 to 29. In 2014, stomach cancer resulted in 0.61% of deaths (13,303 cases) in the U.S. In China, stomach cancer accounted for 3.56% of all deaths (324,439 cases). The highest rate of stomach cancer was in
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 ...
, at 28 cases per 100,000 people. In the United Kingdom, stomach cancer is the 15th-most common cancer (around 7,100 people were diagnosed with stomach cancer in 2011), and it is the 10th-most common cause of cancer-related deaths (around 4,800 people died in 2012). Incidence and mortality rates of gastric cancer vary greatly in Africa. The GLOBOCAN system is currently the most widely used method to compare these rates between countries, but African incidence and mortality rates are seen to differ among countries, possibly due to the lack of universal access to a registry system for all countries. Variation as drastic as estimated rates from 0.3/100000 in Botswana to 20.3/100000 in Mali have been observed. In Uganda, the incidence of gastric cancer has increased from the 1960s measurement of 0.8/100000 to 5.6/100000. Gastric cancer, though present, is relatively low when compared to countries with high incidence like Japan and China. One suspected cause of the variation within Africa and between other countries is due to different strains of the ''H. pylori'' bacteria. The trend commonly seen is that ''H. pylori ''infection increases the risk for gastric cancer, but this is not the case in Africa, giving this phenomenon the name the "African enigma". Although this bacterial species is found in Africa, evidence has supported that different strains with mutations in the bacterial genotype may contribute to the difference in cancer development between African countries and others outside the continent. Increasing access to health care and treatment measures have been commonly associated with the rising incidence, though, particularly in Uganda.


Other animals

The stomach is a muscular organ of the gastrointestinal tract that holds food and begins the digestive process by secreting gastric juice. The most common cancers of the stomach are adenocarcinomas, but other histological types have been reported. Signs vary, but may include vomiting (especially if blood is present), weight loss, anemia, and lack of appetite. Bowel movements may be dark and tarry in nature. To determine whether cancer is present in the stomach, special X-rays and/or abdominal ultrasounds may be performed. Gastroscopy, a test using an endoscope to examine the stomach, is a useful diagnostic tool that can also take samples of the suspected mass for histopathological analysis to confirm or rule out cancer. The most definitive method of cancer diagnosis is through open surgical biopsy. Most stomach tumors are malignant with evidence of spread to lymph nodes or liver, making treatment difficult. Except for lymphoma, surgery is the most frequent treatment option for stomach cancers but it is associated with significant risks.


References


External links

* {{DEFAULTSORT:Stomach Cancer Abdomen Epstein–Barr virus–associated diseases Infectious causes of cancer Wikipedia medicine articles ready to translate