stomach cancer stomach 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. lymphomas and mesenchymal tumors may also develop in the stomach. early symptoms may include heartburn, upper abdominal pain, nausea, and loss of appetite. later signs and symptoms may include weight loss, yellowing of the skin and whites of the eyes, vomiting, 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, lungs, bones, lining of the abdomen, and lymph nodes. stomach cancerother namesgastric cancera stomach ulcer that was diagnosed as cancer on biopsy and surgically removedspecialtygastroenterology oncologysymptomsearly: heartburn, bloating, upper abdominal pain, nausea, belching, loss of appetite.later: weight loss, yellowing of the skin and whites of the eyes, vomiting blood, difficulty swallowing, blood in the stoolusual onsetover yearstypesgastric carcinomas, lymphoma, mesenchymal tumorcauseshelicobacter pylori, geneticsrisk factorssmoking, dietary factors such as pickled vegetables, obesitydiagnostic methodbiopsy done during endoscopypreventionmediterranean diet, stopping smokingtreatmentsurgery, chemotherapy, radiation therapy, targeted therapyprognosisfive-year survival rate:< 10% (advanced cases),32% (us), 71% (japan)frequency3.5 million (2015)deaths783,000 (2018) the most common cause is infection by the bacterium 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 are other risk factors. about 10% of cases run in families, and between 1% and 3% of cases are due to genetic syndromes inherited such as hereditary diffuse gastric cancer. most of the time, stomach cancer develops in stages over years. diagnosis is usually by biopsy done during endoscopy. this is followed by medical imaging to determine if the disease has spread to other parts of the body. japan and south korea, 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, radiation therapy, and targeted therapy. for certain subtypes of gastric cancer, cancer immunotherapy is an option as well. if treated late, palliative care 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 and eastern europe. it occurs twice as often in males as in females. signs and symptoms endoscopic image of linitis plastica, a type of stomach cancer where the entire stomach is invaded, leading to a leather bottle-like appearance with blood coming out of it endoscopic images of the stomach cancer in early stage. its histology was poorly differentiated adenocarcinoma with signet ring cells. left above: normal, right above: fice, left low: acetate stained, right low: aim stained stomach cancer is often either asymptomatic (producing no noticeable symptoms) or it may cause only nonspecific symptoms (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 or a burning sensation (heartburn). 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, fatigue, bloating of the stomach after meals, abdominal pain in the upper abdomen, nausea and occasional vomiting. further enlargement may cause weight loss or bleeding with vomiting blood or having blood in the stool, the latter apparent as black discolouration (melena) and sometimes leading to anemia. dysphagia suggests a tumour in the cardia or extension of the gastric tumour into the esophagus. 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 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, the action of h. pylori virulence factors such as caga, or an interaction between h. pylori infection and germline pathogenic variants in homologous-recombination genes. it was estimated that epstein–barr virus is responsible for 84,000 cases per year. aids 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 sequence of 123-iodine human scintiscans after an intravenous injection: (from left) after 30 minutes, 20 hours, and 48 hours - a high and rapid concentration of radio-iodine is evident in gastric mucosa of the stomach, in salivary glands, oral mucosa, and the periencephalic and cerebrospinal fluid (left). in the thyroid gland, i-concentration is more progressive, also in the reservoir (from 1% after 30 minutes to 5.8% after 48 hours, of the total injected dose). 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, pickled vegetables, and brackens 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 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 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 such as hereditary diffuse gastric cancer. a genetic risk factor for gastric cancer is a genetic defect of the cdh1 gene known as hereditary diffuse gastric cancer (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 changes involved in stomach cancer. a very small percentage of diffuse-type gastric cancers (see histopathology below) arise from an inherited abnormal cdh1 gene. genetic testing and treatment options are available for families at risk. other other risk factors include diabetes, pernicious anemia, chronic atrophic gastritis, menetrier's disease (hyperplastic, hypersecretory gastropathy), and intestinal metaplasia. in addition, foxp3 polymorphism (rs3761548) might contribute to gastric cancer 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 (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-style breath test intended to diagnose stomach cancer by analyzing exhaled chemicals without the need for an intrusive endoscopy. a larger-scale clinical trial of this technology was completed in 2014. abnormal tissue seen in a gastroscope examination is biopsied by the surgeon or gastroenterologist. this tissue is then sent to a pathologist 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 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 to check for anaemia, and a fecal occult blood test to check for blood in the stool. histopathology stomach cancer types by relative incidence gastric adenocarcinoma 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 submucosa and then the muscularis propria. 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,