Stomach cancer

Template:Short description Template:Cs1 config Template:Use dmy dates Template:Infobox medical condition (new) Stomach cancer, also known as gastric cancer, is a malignant tumor of the stomach. It is a cancer that develops in the lining of the stomach, caused by abnormal cell growth.<ref>Template:Cite web</ref> Most cases of stomach cancers are gastric carcinomas, which can be divided into several subtypes, including gastric adenocarcinomas.<ref name=WCR2014/> Lymphomas and mesenchymal tumors may also develop in the stomach.<ref name=WCR2014/> Early symptoms may include heartburn, upper abdominal pain, nausea, and loss of appetite.<ref name=NCI2014TxPt/> 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.<ref name="NCI2014TxPt">Template:Cite web</ref> 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.<ref>Template:Cite book</ref>

The bacterium Helicobacter pylori accounts for more than 60% of cases of stomach cancer.<ref name=WCR2014/><ref name=ChangParsonnet2010>Template:Cite journal</ref><ref>Template:Cite book</ref> Certain strains of H. pylori have greater risks than others.<ref name=WCR2014/> Smoking, dietary factors such as pickled vegetables and obesity are other risk factors.<ref name="WCR2014" /><ref name="pmid24011243">Template:Cite journal</ref> 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.<ref name=WCR2014/> Most of the time, stomach cancer develops in stages over the years.<ref name=WCR2014/> Diagnosis is usually by biopsy done during endoscopy.<ref name=NCI2014TxPt/> This is followed by medical imaging to determine if the cancer has spread to other parts of the body.<ref name=NCI2014TxPt/> Japan and South Korea, two countries that have high rates of the disease, screen for stomach cancer.<ref name=WCR2014/>

A Mediterranean diet lowers the risk of stomach cancer, as does not smoking.<ref name=WCR2014/><ref name=NCI2014Prevent/> Tentative evidence indicates that treating H. pylori decreases the future risk.<ref name=WCR2014/><ref name=NCI2014Prevent>Template:Cite web</ref> If stomach cancer is treated early, it can be cured.<ref name=WCR2014/> Treatments may include some combination of surgery, chemotherapy, radiation therapy, and targeted therapy.<ref name=NCI2014TxPt/><ref name=Wagner17>Template:Cite journal</ref> For certain subtypes of gastric cancer, cancer immunotherapy is an option as well.<ref>Template:Cite journal</ref> If treated late, palliative care may be advised.<ref name=WCR2014/> Some types of lymphoma can be cured by eliminating H. pylori.<ref name=St2010>Template:Cite journal</ref> Outcomes are often poor, with a less than 10% five-year survival rate in the Western world for advanced cases.<ref name = WJG14/> This is largely because most people with the condition present with advanced disease.<ref name=WJG14>Template:Cite journal</ref> In the United States, five-year survival is 31.5%,<ref name=SEER2020>Template:Cite web</ref> while in South Korea it is over 65% and Japan over 70%, partly due to screening efforts.<ref name=WCR2014/><ref name=Jap2011>Template:Cite web</ref>

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.<ref name=WCR2014Epi>Template:Cite book</ref> In 2018, it newly occurred in 1.03 million people and caused 783,000 deaths.<ref name=Bray2018>Template:Cite journal</ref> Before the 1930s, it was a leading cause of cancer deaths in the Western world; rates have sharply declined among younger generations in the West, although they remain high for people living in East Asia.<ref>Template:Cite book</ref><ref>Template:Cite book</ref><ref>Template:Cite bookTemplate:Self-published inline</ref> The decline in the West is believed to be due to the decline of salted and pickled food consumption, as a result of the development of refrigeration as a method of preserving food.<ref>Template:Cite book</ref> Stomach cancer occurs most commonly in East Asia, followed by Eastern Europe.<ref name=WCR2014/> It occurs twice as often in males as in females.<ref name=WCR2014>Template:Cite book</ref>

Signs and symptoms

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

Endoscopic image of linitis plastica, where the entire stomach is invaded with cancer, leading to a leather bottle like appearance and congealed pus and blood

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.<ref name="SAOGC">Template:Cite web</ref> Stomach cancer can cause the following signs and symptoms: Unexplained nausea, vomiting, diarrhoea, and constipation. Patients can also experience unexplained weight loss.<ref>Template:Cite journal</ref>

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.<ref>Template:Cite web</ref> Abdominal discomfort and loss of appetite can occur.<ref>Template:Cite web</ref><ref>Template:Cite journal</ref>

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.Template:Citation needed

These can be symptoms of other problems such as a stomach virus, gastric ulcer, or tropical sprue.Template:Citation needed

Risk factors

Gastric cancer can occur as a result of many factors.<ref>Template:Cite journal</ref> It occurs twice as commonly in males as females. Estrogen may protect women against the development of this form of cancer.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>

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.<ref name="pmid24011243" /><ref name="GVRF-4">Template:Cite web</ref> The mechanism by which H. pylori induces stomach cancer potentially involves chronic inflammation, the action of H. pylori virulence factors such as CagA,<ref name="pmid16367902">Template:Cite journal</ref> or an interaction between H. pylori infection and germline pathogenic variants in homologous-recombination genes.<ref>Template:Cite journal</ref> It was estimated that Epstein–Barr virus is responsible for 84,000 cases per year.<ref>Template:Cite web</ref> AIDS is also associated with elevated risk.<ref name="pmid24011243"/>

Smoking

Smoking increases the risk of developing gastric cancer significantly, from a 40% increased risk for people who currently smoke to an 82% increase for people who smoke heavily. Gastric cancers due to smoking mostly occur in the upper part of the stomach near the esophagus.<ref name=ACS_Risk/><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>

Alcohol

Some studies show increased risk with alcohol consumption as well.<ref name="pmid24011243"/><ref name="pmid24191271">Template:Cite journal</ref>

Diet

Dietary factors are not proven causes, and the association between stomach cancer and various foods and beverages is weak.<ref name="Theodoratou2017">Template:Cite journal</ref> Some foods including fried foods,<ref>Template:Cite journal</ref> smoked foods, salt and salt-rich foods, meat,<ref name=ferro-meat>Template:Cite journal</ref> processed meat,<ref name=ferro-meat /> red meat,<ref name=ferro-meat /> pickled vegetables, and brackens<ref>Template:Cite journal</ref> are associated with a higher risk of stomach cancer.<ref name="pmid24011243"/><ref name="pmid16865769">Template:Cite journal</ref>

Fresh fruit and vegetable intake,<ref name=ferro-fruits>Template:Cite journal</ref> citrus fruit intake,<ref name=ferro-fruits /> and antioxidant intake are associated with a lower risk of stomach cancer.<ref name="pmid24011243"/><ref name=ACS_Risk>Template:Cite web</ref> A Mediterranean diet is associated with lower rates of stomach cancer,<ref name="American Journal of Clinical Nutrition">Template:Cite journal</ref> as is regular aspirin use.<ref name="pmid24011243"/>

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).<ref name="crew">Template:Cite journal</ref> 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.<ref name="hamp">Template:Cite journal</ref> However, the risk of gastric cardia adenocarcinoma, with GERD present, has been found to increase more than two times for an obese person.<ref name="crew"/> There is a correlation between iodine deficiency and gastric cancer.<ref>Template:Cite book</ref>

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.<ref name=WCR2014/>

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.<ref name="chel"/> When the gene experiences a particular mutation, gastric cancer develops through a mechanism that is not fully understood.<ref name="chel">Template:Cite web</ref><ref>Template:Cite journal</ref> This mutation is considered autosomal dominant, meaning that half of a carrier's children will likely experience the same mutation.<ref name="chel"/> 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.<ref name="chel"/> The diagnosis can also be made if at least three cases occur in the family, in which case age is not considered.<ref name="chel"/>

The International Cancer Genome Consortium is leading efforts to identify genomic changes involved in stomach cancer.<ref name="ICGC-USA">Template:Cite web</ref><ref name="ICGC-China">Template:Cite web</ref> 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.<ref name="pmid15235021">Template:Cite journal</ref>

Bile reflux

Bile reflux, in addition to Helicobacter pylori infection, is a pathogenic factor in gastric intestinal metaplasia, a precancerous lesion of gastric cancer.<ref>Template:Cite journal</ref> Long-term irritation of the gastric mucosa caused by bile reflux appears to have a role in gastric carcinogenesis.<ref name = Lei2023>Template:Cite journal</ref> Bile acids, which are a significant component of bile reflux, may be a causal factor in gastric carcinogenesis.<ref name = Lei2023/>

Diagnosis

A stomach ulcer that was diagnosed as cancer on biopsy

To find the cause of symptoms, the doctor asks about the patient's medical history, does a physical examination, and may order laboratory studies.<ref>Template:Cite web</ref> 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.<ref name="pmid24191271"/>
• 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.<ref>Template:Cite journal</ref>

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.<ref>Template:Cite journal</ref><ref>Template:Cite web</ref> A larger-scale clinical trial of this technology was completed in 2014.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>

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.<ref name="pmid24191271"/>

Various gastroscopic modalities have been developed to increase the 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 investigatively for similar applications.<ref>Template:Cite journal</ref>

Several skin 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.<ref name="pmid15230897">Template:Cite journal</ref>

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.<ref>Template:Cite journal</ref>

Histopathology

Stomach cancer types by relative incidence<ref>Template:Cite journal</ref>

• Gastric adenocarcinoma is a malignant epithelial tumour, originating from glandular epithelium of the gastric mucosa. Stomach cancers are about 90% adenocarcinomas.<ref>Template:Cite book</ref> 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, and reduced stroma ("back to back" aspect). Often, it is associated with 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.Template:Citation needed
• Around 5% of gastric cancers are lymphomas.<ref>Template:Cite book</ref> These may include extranodal marginal zone B-cell lymphomas (MALT type)<ref name=Bur2017>Template:Cite journal</ref> and to a lesser extent diffuse large B-cell lymphomas.<ref name="pmid25052386">Template:Cite journal</ref> MALT type make up about half of stomach lymphomas.<ref name=St2010/>
• Carcinoid and stromal tumors may occur.Template:Citation needed

• 
  Poor to moderately differentiated adenocarcinoma of the stomach. H&E stain.
• 
  Gastric signet ring cell carcinoma. H&E stain.
• 
  Adenocarcinoma of the stomach and intestinal metaplasia. H&E stain.

Staging

T stages of stomach cancer

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,<ref name="pmid16418249">Template:Cite journal</ref> an endoscopic ultrasound exam, or other tests to check these areas. Blood tests for tumor markers, such as carcinoembryonic antigen and carbohydrate antigen, may be ordered, as their levels correlate with the extent of metastasis, especially to the liver, and the cure rate.Template:Citation needed

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.Template:Citation needed

The clinical stages of stomach cancer are:<ref>Template:Cite web</ref><ref>Template:Cite web</ref>

• 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 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 (stage 1B): Stage 1A is treated by surgery, including removal of the omentum. Stage 1B may be treated with chemotherapy (5-fluorouracil) 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.
• 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.<ref name=Wagner17/>

Stomach cancer metastasized to the lungs

The TNM staging system is also used.<ref>Template:Cite web</ref>

In a study of open-access endoscopy in Scotland, patients were diagnosed 7% in stage I, 17% in stage II, and 28% in stage III.<ref>Template:Cite journal</ref> A Minnesota population was diagnosed 10% in stage I, 13% in stage II, and 18% in stage III.<ref>Template:Cite journal</ref> However, in a high-risk population in the Valdivia Province of southern Chile, only 5% of patients were diagnosed in the first two stages and 10% in stage III.<ref name=Valdivia>Template:Cite journal</ref>

Prevention

Getting rid of H. pylori in those who are infected decreases the risk of stomach cancer.<ref>Template:Cite journal</ref> A 2014 meta-analysis of observational studies found that a diet high in fruits, mushrooms, garlic, soybeans, and green onions was associated with a lower risk of stomach cancer in the Korean population.<ref name=Woo2014>Template:Cite journal</ref> Low doses of vitamins, especially from a healthy diet, decrease the risk of stomach cancer.<ref>Template:Cite journal</ref> A previous review of antioxidant supplementation did not find supporting evidence and possibly worse outcomes.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> Modern technology is used to promote early diagnosis, e.g. based on serum markers.<ref>Template:Cite journal</ref> Recent reviews have begun to explore the potential role of naturally derived compounds, such as diterpenes, in the prevention and treatment of gastric cancer.<ref>Ma C, Gao L, Song K, Gu B, Wang B, Pu W, Chen H. Exploring the therapeutic potential of diterpenes in gastric cancer: Mechanisms, efficacy, and clinical prospects. Biomolecules and Biomedicine. 2025;25(1):1–15.</ref>

Management

A gross anatomy specimen of a total gastrectomy, splenectomy for infiltrative gastric cancer

The same picture, close-up, total gastrectomy, infiltrative gastric cancer

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.<ref name="pmid23639645">Template:Cite journal</ref>

Treatment for stomach cancer may include surgery,<ref name="pmid23983442">Template:Cite journal</ref> chemotherapy,<ref name=Wagner17 /> or radiation therapy.<ref name="pmid23622077">Template:Cite journal</ref> New treatment approaches such as immunotherapy or gene therapy and improved ways of using current methods are being studied in clinical trials.<ref name="pmid21556317">Template:Cite journal</ref>

Surgery

Anatomy before Roux-en-y surgery to resect stomach cancer

Surgery remains the only curative therapy for stomach cancer.<ref name="WJG14"/> A 2016 Cochrane review 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.<ref>Template:Cite journal</ref> Post-operatively, up to 70% of people undergoing total gastrectomy develop complications such as dumping syndrome and reflux esophagitis.<ref name=":0">Template:Cite journal</ref>

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.<ref name=":0" /> Proximal gastrectomy can be considered a viable alternative for upper third early gastric cancer.<ref name="Narayan2024">Template:Cite journal</ref> Of the different surgical techniques, endoscopic mucosal resection is a treatment for early gastric cancer in which the tumor within the mucosa is removed using an electrical wire loop through the endoscope, providing a much smaller operation than removing the stomach.<ref name = "deyhle1974">Template:Cite journal</ref><ref name = WJG14/> Endoscopic submucosal dissection is a similar technique used to resect a large area of mucosa in one piece.<ref name = WJG14/> If the pathology examination of the resected specimen shows incomplete resection or deep invasion by tumor, the patient would need a formal stomach resection.<ref name = WJG14/> Uncut Roux-en-Y reconstruction after distal gastrectomy shows similar rates of major complications and anastomotic leakage compared with Billroth II and standard Roux-en-Y reconstruction. It may reduce the risk of bile reflux compared with Billroth II but increase it compared with Roux-en-Y.<ref>Cai H, Li Y, Wu X, et al. (June 2024). "Uncut Roux-en-Y reconstruction versus Billroth II and Roux-en-Y reconstruction after distal gastrectomy for gastric cancer". Cochrane Database of Systematic Reviews. 2024(6): CD014943. doi:https://doi.org/10.1002/14651858.CD015014.pub2. PMID 38956467.</ref>

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.<ref name = WJG14/><ref>Template:Cite journal</ref>

Chemotherapy

Combination chemotherapy has been shown to improve overall survival compared with best supportive care in advanced gastric cancer, although the benefit remains modest and treatment is associated with increased toxicity.<ref>Nishizaki M, Syn NL, Wang L, Yoshikawa T, Lu Z, Gao TS, et al. (May 2021). "Chemotherapy versus best supportive care for advanced gastric cancer". The Cochrane Database of Systematic Reviews. 2021 (5): CD012188. doi:10.1002/14651858.CD012188.pub2</ref> The use of chemotherapy to treat stomach cancer has no firmly established standard of care.<ref name=Wagner17 /> 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.<ref name=Wagner17 /> Some drugs used in stomach cancer treatment have included: fluorouracil or its analog capecitabine, BCNU (carmustine), methyl-CCNU (semustine) and doxorubicin (Adriamycin), as well as mitomycin C, and more recently cisplatin and taxotere, often using drugs in various combinations.<ref name=Wagner17/> The relative benefits of these different drugs, alone and in combination, are unclear.<ref name=Wagner17 /><ref name="pmid17425475">Template:Cite journal</ref> 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.<ref name = WJG14/>

Targeted therapy

Treatment with the human epidermal growth factor receptor 2 (HER2) inhibitor trastuzumab has been demonstrated to increase overall survival in inoperable locally advanced or metastatic gastric carcinoma over-expressing the HER2/neu gene.<ref name="WJG14" /> In particular, HER2 is overexpressed in 13–22% of patients with gastric cancer.<ref name="pmid21556317" /><ref name=Fusco13>Template:Cite journal</ref> 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.<ref name=Fusco13 />

A recent clinical study reported promising results for a combination therapy using nivolumab and catequentinib (anlotinib) in the treatment of advanced gastric adenocarcinoma (GAC) and esophageal squamous cell carcinoma (ESCC), that improve the immune response against cancer while simultaneously slowing tumor progression.<ref>Template:Cite journal</ref> The research, conducted by Zhongshan Hospital, Fudan University, and BGI Genomics, was published in Nature Communications in October 2024. The study evaluated the efficacy of combining Nivolumab, an immunotherapy that enhances the immune system's ability to attack cancer cells, with anlotinib hydrochloride, a drug that inhibits tumor angiogenesis by blocking signals essential for the growth of new blood vessels.<ref>Template:Cite web</ref>

Radiation

Radiation therapy (also called radiotherapy) may be used to treat stomach cancer, often as an adjuvant to chemotherapy and/or surgery.<ref name = WJG14/>

Lymphoma

MALT lymphomas are often completely resolved after the underlying H. pylori infection is treated.<ref name=St2010/> This results in remission in about 80% of cases.<ref name=St2010/>

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.<ref name=MSR>Template:EMedicine</ref> The average life expectancy after being diagnosed is around 24 months, and the five-year survival rate for stomach cancer is less than 10%.<ref name = WJG14/>

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.<ref name="atlas">Template:Cite web</ref><ref>Template:Cite journal</ref> Examples of poor prognosis genes include ITGAV, DUSP1 and P2RX7.<ref>Template:Cite journal</ref>

Epidemiology

Stomach cancer deaths per million persons in 2012 Template:Div colTemplate:LegendTemplate:LegendTemplate:LegendTemplate:LegendTemplate:LegendTemplate:LegendTemplate:LegendTemplate:LegendTemplate:LegendTemplate:LegendTemplate:Div col end

In 2018, stomach cancer was the fifth most frequently diagnosed cancer worldwide, representing 5.7% of all cancer cases, and the third leading cause of death from cancers, being responsible for 8.2% of all cancer deaths.<ref name=":1">Template:Cite book</ref> Among men, 683,754 cases were diagnosed, accounting for 7.2% of all cancer cases, and among women, stomach cancer was diagnosed in 349,947 cases, accounting for 4.1% of all cancer cases.<ref name=":1" />

In 2012, stomach cancer was the fifth most-common cancer with 952,000 cases diagnosed.<ref name="WCR2014Epi" /> It is more common both in men and in developing countries.<ref name="Parkin">Template:Cite journal</ref><ref name="WHO-QA15">Template:Cite web</ref> In 2012, it represented 8.5% of cancer cases in men, making it the fourth most-common cancer in men.<ref>Template:Cite book</ref> 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 and liver cancer).<ref name="Loz2012">Template:Cite journal</ref><ref>Template:Cite web</ref>

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.<ref>Template:Cite journal</ref>

In 2014, stomach cancer resulted in 0.61% of deaths (13,303 cases) in the United States.<ref>Template:Cite web</ref> In China, stomach cancer accounted for 3.56% of all deaths (324,439 cases).<ref>Template:Cite web</ref>Template:Unreliable source? The highest rate of stomach cancer was in Mongolia, at 28 cases per 100,000 people.<ref>Template:Cite web</ref>Template:Unreliable source?

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).<ref>Template:Cite web</ref>

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.<ref name="asom">Template:Cite journal</ref> Variation as drastic as estimated rates from 0.3/100000 in Botswana to 20.3/100000 in Mali have been observed.<ref name="asom"/> In Uganda, the incidence of gastric cancer has increased from the 1960s measurement of 0.8/100000 to 5.6/100000.<ref name="asom"/> 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".<ref name="louw">Template:Cite journal</ref> 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.<ref name="louw"/> Increasing access to health care and treatment measures have been commonly associated with the rising incidence, though, particularly in Uganda.<ref name="asom"/>

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.<ref name=MacEwan_2013>Template:Cite book</ref>

External links

• Template:Cite web