Stomach cancer

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Key Terms: Adenocarcinoma, Anemia, Barium x ray, Biopsy, Chemotherapy, Endoscopic ultrasound, External radiation therapy, Infiltrate, Polyp, Radiation therapy, Total gastrectomy.

Definition

Stomach cancer (also known as gastric cancer) is a disease in which the cells forming the inner lining of the stomach become abnormal and start to divide uncontrollably, forming a mass called a tumor.

Description

The stomach is a J-shaped organ that lies in the left and central portion of the abdomen. The stomach produces many digestive juices and acids that mix with the food and aid in the process of digestion. There are five regions of the stomach that doctors refer to when determining the origin of stomach cancer. These are:

• the cardia, area surrounding the cardiac sphincter which controls movement of food from the esophagus into the stomach;
• the fundus, upper expanded area adjacent to the cardiac region;
• the antrum, lower region of the stomach where it begins to narrow;
• the prepyloric, region just before or nearest the pylorus;
• and the pylorus, the terminal region where the stomach joins the small intestine. Cancer can develop in any of the five sections of the stomach. Symptoms and outcomes of the disease will vary depending on the location of the cancer.

Demographics

Based on previous data from the National Cancer Institute and the United States Census, the American Cancer Society estimates that 21,700 Americans will be diagnosed with stomach cancer during 2001 and approximately 13,000 deaths will result from the disease. In most areas, men are affected by stomach cancer nearly twice as often as women. Most cases of stomach cancer are diagnosed between the ages of 50 and 70 but in families with a hereditary risk of stomach cancer, younger cases are more frequently seen.

Stomach cancer is one of the leading causes of cancer deaths in several areas of the world, most notably Japan and other Asian countries. In Japan it appears almost ten times as frequently as in the United States. The number of new stomach cancer cases is decreasing in some areas, however, especially in developed countries. In the United States, incidence rates have dropped from 30 individuals per 100,000 in the 1930s, to only 8 in 100,000 individuals developing stomach cancer by the 1980s. The use of refrigerated foods and increased consumption of fresh fruits and vegetables, instead of preserved foods with high salt content, may be a reason for the decline.

Causes and Symptoms

While the exact cause for stomach cancer has not been identified, several potential factors have lead to increased numbers of individuals developing the disease and therefore, significant risk has been associated. Diet, work environment, exposure to the bacterium Helicobacter pylori, and a history of stomach disorders such as ulcers or polyps are some of these believed causes.

Studies have shown that eating foods with high quantities of salt and nitrites increases the risk of stomach cancer. The diet in a specific region can have a great impact on its residents. Making changes to the types of foods consumed has been shown to decrease likelihood of disease, even for individuals from countries with higher risk. For example, Japanese people who move to the United States or Europe and change the types of foods they eat have a far lower chance of developing the disease than do Japanese people who remain in Japan and do not change their dietary habits. Eating recommended amounts of fruit and vegetables may lower a person's chances of developing this cancer.

A high risk for developing stomach cancers has been linked to certain industries as well. The best proven association is between stomach cancer and persons who work in coal mining and those who work processing timber, nickel, and rubber. An unusually large number of these workers have been diagnosed with this form of cancer.

Several studies have identified a bacterium (Helicobacter pylori) that causes stomach ulcers (inflammation in the inner lining of the stomach). Chronic (long-term) infection of the stomach with these bacteria may lead to a particular type of cancer (lymphomas or mucosa-associated lymphoid tissue [MALT]) in the stomach.

Another risk factor is the development of polyps, benign growths in the lining of the stomach. Although polyps are not cancerous, some may have the potential to turn cancerous. People in blood group A are also at elevated risk for this cancer for unknown reasons. Other speculative causes of stomach cancer include previous stomach surgery for ulcers or other conditions, or a form of anemia known as pernicious anemia.

Stomach cancer is a slow-growing cancer. It may be years before the tumor grows very large and produces distinct symptoms. In the early stages of the disease, the patient may only have mild discomfort, indigestion, heartburn, a bloated feeling after eating, and mild nausea. In the advanced stages, a patient will have loss of appetite and resultant weight loss, stomach pains, vomiting, difficulty in swallowing, and blood in the stool. Stomach cancer often spreads (metastasizes) to adjoining organs such as the esophagus, adjacent lymph nodes, liver, or colon.

Diagnosis

Unfortunately, many patients diagnosed with stomach cancer experience pain for two or three years before informing a doctor of their symptoms. When a doctor suspects stomach cancer from the symptoms described by the patient, a complete medical history will be taken to check for any risk factors. A thorough physical examination will be conducted to assess all the symptoms. Laboratory tests may be ordered to check for blood in the stool (fecal occult blood test) and anemia (low red blood cell count), which often accompany gastric cancer.

In some countries, such as Japan, it is appropriate for patients to be given routine screening examinations for stomach cancer, as the risk of developing cancer in that society is very high. Such screening might be useful for all high-risk populations. Due to the low prevalence of stomach cancer in the United States, routine screening is usually not recommended unless a family history of the disease exists.

Whether as a screening test or because a doctor suspects a patient may have symptoms of stomach cancer, endoscopy or barium x rays are used in diagnosing stomach cancer. For a barium x ray of the upper gastrointestinal tract, the patient is given a chalky, white solution of barium sulfate to drink. This solution coats the esophagus, the stomach, and the small intestine. Air may be pumped into the stomach after the barium solution in order to get a clearer picture. Multiple x rays are then taken. The barium coating helps to identify any abnormalities in the lining of the stomach.

In another more frequently used test, known as upper gastrointestinal endoscopy, a thin, flexible, lighted tube (endoscope) is passed down the patient's throat and into the stomach. The doctor can view the lining of the esophagus and the stomach through the tube. Sometimes, a small ultrasound probe is attached at the end of the endoscope. This probe sends high frequency sound waves that bounce off the stomach wall. A computer creates an image of the stomach wall by translating the pattern of echoes generated by the reflected sound waves. This procedure is known as an endoscopic ultra-sound or EUS.

Endoscopy has several advantages, in that the physician is able to see any abnormalities directly. In addition, if any suspicious-looking patches are seen, biopsy forceps can be passed painlessly through the tube to collect some tissue for microscopic examination. This is known as a biopsy. EUS is beneficial because it can provide valuable information on depth of tumor invasion.

After stomach cancer has been diagnosed and before treatment starts, another type of x-ray scan is taken. Computed tomography (CT) is an imaging procedure that produces a three-dimensional picture of organs or structures inside the body. CT scans are used to obtain additional information in regard to how large the tumor is and what parts of the stomach it borders; whether the cancer has spread to the lymph nodes; and whether it has spread to distant parts of the body (metastasized), such as the liver, lung, or bone. A CT scan of the chest, abdomen, and pelvis is taken. If the tumor has gone through the wall of the stomach and extends to the liver, pancreas, or spleen, the CT will often show this. Although a CT scan is an effective way of evaluating whether cancer has spread to some of the lymph nodes, it is less effective than EUS in evaluating whether the nodes closest to the stomach are free of cancer. However, CT scans, like barium x-rays, have the advantage of being less invasive than upper endoscopy.

Laparoscopy is another procedure used to stage some patients with stomach cancer. This involves a medical device similar to an endoscope. A laparoscopy is a minimally invasive surgery technique with one or a few small incisions, which can be performed on an outpatient basis, followed by rapid recovery. Patients who may receive radiation therapy or chemotherapy before surgery may undergo a laparoscopic procedure to determine the precise stage of cancer. The patient with bone pain or with certain laboratory results should be given a bone scan.

Benign gastric neoplasms are tumors of the stomach that cause no major harm. One of the most common is called a submucosal leiomyoma. If a leiomyoma starts to bleed, surgery should be performed to remove it. However, many leiomyomas require no treatment. Diagnosis of stomach cancers should be conducted carefully so that if the tumor does not require treatment the patient is not subjected to a surgical operation.

Clinical Staging and Prognosis

More than 95% of stomach cancers are caused by adenocarcinomas, malignant cancers that originate in glandular tissues. The remaining 5% of stomach cancers include lymphomas and other types of cancers. It is important that gastric lymphomas be accurately diagnosed because these cancers have a much better prognosis than stomach adenocarcinomas. Approximately half of the people with gastric lymphomas survive five years after diagnosis. Treatment for gastric lymphoma involves surgery combined with chemotherapy and radiation therapy.

Staging of stomach cancer is based on how deep the growth has penetrated the stomach lining; to what extent (if any) it has invaded surrounding lymph nodes; and to what extent (if any) it has spread to distant parts of the body (metastasized). The more confined the cancer, the better the chance for a cure.

One important factor in the staging of adenocarcinoma of the stomach is whether or not the tumor has invaded the surrounding tissue and, if it has, how deep it has penetrated. If invasion is limited, prognosis is favorable. Diseased tissue that is more localized improves the outcome of surgical procedures performed to remove the diseased area of the stomach. This is called a resection of the stomach.

Several distinct ways of classifying stomach cancer according to cell type have been proposed. The Lauren classification is encountered most frequently. According to this classification system, gastric adenocarcinomas are either called intestinal or diffuse. Intestinal cancers are much like a type of intestinal cancer called intestinal carcinoma. Intestinal tumors are more frequently found in males and in older patients. The prognosis for these tumors is better than that for diffuse tumors. Diffuse tumors are more likely to infiltrate, that is, to move into another organ of the body.

Treatment

Because symptoms of stomach cancer are so mild, treatment often does not commence until the disease is well advanced. The three standard modes of treatment for stomach cancer include surgery, radiation therapy, and chemotherapy. While deciding on the patient's treatment plan, the doctor takes into account many factors. The location of the cancer and its stage are important considerations. In addition, the patient's age, general health status, and personal preferences are also taken into account.

Surgery

In the early stages of stomach cancer, surgery may be used to remove the cancer. Surgical removal of adenocarcinoma is the only treatment capable of eliminating the disease. Laparoscopy is often used before surgery to investigate whether or not the tumor can be removed surgically. If the cancer is widespread and cannot be removed with surgery, an attempt will be made to remove blockage and control symptoms such as pain or bleeding. Depending on the location of the cancer, a portion of the stomach may be removed, a procedure called a partial gastrectomy. In a surgical procedure known as total gastrectomy, the entire stomach may be removed. However, doctors prefer to leave at least part of the stomach if possible. Patients who have been given a partial gastrectomy achieve a better quality of life than those having a total gastrectomy and typically lead normal lives. Even when the entire stomach is removed, the patients quickly adjust to a different eating schedule. This involves eating small quantities of food more frequently. High protein foods are generally recommended.

Partial or total gastrectomy is often accompanied by other surgical procedures. Lymph nodes are frequently removed and nearby organs, or parts of these organs, may be removed if cancer has spread to them. Such organs may include the pancreas, colon, or spleen.

Preliminary studies suggest that patients who have tumors that cannot be removed by surgery at the start of therapy may become candidates for surgery later. Combinations of chemotherapy and radiation therapy are sometimes able to reduce disease for which surgery is not initially appropriate. Preliminary studies are being performed to determine if some of these patients can become candidates for surgical procedures after such therapies are applied.

Chemotherapy

Whether or not patients undergoing surgery for stomach cancer should receive chemotherapy is a controversial issue. Chemotherapy involves administering anti-cancer drugs either intravenously (through a vein in the arm) or orally (in the form of pills). This can either be used as the primary mode of treatment or after surgery to destroy any cancerous cells that may have migrated to distant sites. Most cancers of the gastrointestinal tract do not respond well to chemotherapy, however, adenocarcinoma of the stomach and advanced stages of cancer are exceptions.

Chemotherapy medicines such as doxorubicin, mitomycin C, and 5-fluorouracil (5-FU or fluorouracil), used alone, provide benefit to at least one in five patients. Combinations of agents may provide even more benefit, although it is not certain that this includes longer survival. For example, some doctors use what is called the FAM regimen, which combines 5-fluorouacil, doxorubicin, and mitomycin. Some doctors prefer using 5-fluo-rouracil alone to FAM since side effects are more moderate. Another combination some doctors are using involve high doses of the medications methotrexate, 5- fluorouracil, and doxorubicin. Other combinations that have shown benefit include the ELF regimen, a combination of leucovorin, 5-fluorouracil, and etoposide. The EAP regimen, a combination of etoposide, doxorubicin, and cisplatin is also used.

Although chemotherapy using a single medicine is sometimes used, the best response rates are often achieved with combinations of medicines. Therefore, in addition to studies exploring the effectiveness of new medicines there are other studies attempting to evaluate how to best combine existing forms of chemotherapy to bring the greatest degree of help to patients.

Radiation Therapy

Radiation therapy is often used after surgery to destroy the cancer cells that may not have been completely removed during surgery. To treat stomach cancer, external beam radiation therapy is generally used. In this procedure, high-energy rays from a machine that is outside of the body are concentrated on the area of the tumor. In the advanced stages of stomach cancer, radiation therapy is used to ease the symptoms such as pain and bleeding. However, studies of radiation treatment for stomach cancer have shown that the way it has been used it has been ineffective for many patients.

Researchers are actively assessing the role of chemotherapy and radiation therapy used before a surgical procedure is conducted. They are searching for ways to use both chemotherapy and radiation therapy so that they increase the length of survival of patients more effectively than current methods are able to do.

Prognosis

Overall, approximately 20% of patients with stomach cancer live at least five years following diagnosis. Patients diagnosed with stomach cancer in its early stages have a far better prognosis than those for whom it is in the later stages. In the early stages, the tumor is small, lymph nodes are unaffected, and the cancer has not migrated to the lungs or the liver. Unfortunately, only about 20% of patients with stomach cancer are diagnosed before the cancer had spread to the lymph nodes or formed a distant metastasis.

It is important to remember that statistics on prognosis may be misleading. Newer therapies are being developed rapidly and five-year survival has not yet been measured with these. Also, the largest group of people diagnosed with stomach cancer are between 60 and 70 years of age, suggesting that some of these patients die not from cancer but from other age-related diseases. As a result, some patients with stomach cancer may be expected to have longer survival than did patients just ten years ago.

Coping With Cancer Treatment

Many patients experience feelings of depression, anxiety, and fatigue when dealing with the knowledge and treatments associated with stomach cancer. Side effects such as nausea and vomiting may also present during treatment. Understanding what to expect as a result of the various treatments and learning about alternative methods for reducing these symptoms may improve the effectiveness of treatments and provide a more positive outlook in regard to the individual's situation. A doctor or other health professional should be consulted to develop strategies for managing any negative symptoms or feelings.

Prevention

Avoiding many of the risk factors associated with stomach cancer may prevent its development. Excessive amounts of salted, smoked, and pickled foods should be avoided, as should foods high in nitrates. A diet that includes recommended amounts of fruits and vegetables is believed to lower the risk of several cancers, including stomach cancer. The American Cancer Society recommends eating at least five servings of fruits and vegetables daily and choosing six servings of food from other plant sources, such as grains, pasta, beans, cereals, and whole grain bread.

Abstaining from tobacco and excessive amounts of alcohol will reduce the risk for many cancers. In countries where stomach cancer is common, such as Japan, early detection is important for successful treatment.

Questions to Ask the Doctor

• Has the cancer spread to the lymph nodes?
• Has the cancer spread to the lungs, liver, or spleen?
• (After endoscopy or barium x-rays and CT scan have been completed) Would I benefit from endoscopic ultrasound or laparoscopy?
• (If surgery is recommended) Do recent studies show that it might be a good idea to also use chemotherapy or radiation therapy?
• (If gastrectomy or partial gastrectomy was performed) How should I alter my diet and eating patterns?
• (Following surgery) What foods should I be eating? Is there a registered dietitian I can speak with on a regular basis about what I should eat?

Special Concerns

Following gastrectomy or partial gastrectomy it is important for the patient to carefully follow doctor's orders about what foods are eaten and when they should be eaten. In particular, the patient may be asked to have small, frequent meals.

Resources

Books

Braunwald, Eugene, et al. Harrison's Principles of Internal Medicine. 15th ed. New York: McGraw-Hill, 2001.

Herfindal Eric T., and Dick R. Gourley. Textbook of Therapeutics: Drug and Disease Management. 7th ed. Philadelphia: Lippincott Williams & Wilkins, 2000.

Humes, H. David, editor. Kelley's Textbook of Internal Medicine Philadelphia: Lippincott Williams & Wilkins, 2000.

Pazdur, Richard, et al. Cancer Management: A Multidisciplinary Approach: Medical, Surgical, & Radiation Oncology. 4th ed. Melville, NY: PRR, 2000.

Steen, Grant, and Joseph Mirro. Childhood Cancer: A Handbook from St. Jude Children's Research Hospital. Cambridge, MA: Perseus Publishing, 2000.

Organizations

National Coalition for Cancer Survivorship. 1010 Wayne Ave., 7th Floor, Silver Spring, MD 20910-5600. (301) 650-9127 or (877) NCCS-YES. .

Stomach Cancer: Detection and Symptoms. Stomach Cancer: Prevention and Risk Factors. Stomach Cancer: Treatment. Stomach Cancer: What Is It? American Cancer Society. (800) ACS-2345. .

What You Need to Know About Stomach Cancer. PDQ Treatment—Patients: Gastric Cancer. The National Cancer Institute. (800) 4-CANCER. .

—Lata Cherath, Ph.D.; Bob Kirsch

Gastric cancer
Classification and external resources
A suspicious stomach ulcer that was diagnosed as cancer on biopsy and resected. Surgical specimen.
ICD-10	C16
ICD-9	151.9
OMIM	137215
DiseasesDB	12445
eMedicine	med/845
MeSH	D013274

Stomach cancer, or gastric cancer, refers to cancer arising from any part of the stomach. Stomach cancer causes about 800,000 deaths worldwide per year.^[1]

Contents 1 Signs and symptoms 2 Causes 3 Diagnosis 3.1 Histopathology 3.2 Staging 4 Management 4.1 Surgery 4.2 Chemotherapy 4.3 Radiation 4.4 Multimodality therapy 5 Epidemiology 6 In other animals 7 References 8 External links

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 image of early stage of the stomach cancer. Its histology was poorly differentiated adno carcinoma with signet ring cells.Left above=Normal, right above=FICE, left low=acetate stained, right low= AIM stained

Stomach cancer is often asymptomatic or causes only nonspecific symptoms in its early stages. By the time symptoms occur, the cancer has often reached an advanced stage (see below), one of the main reasons for its poor prognosis.^{[citation needed]} Stomach cancer can cause the following signs and symptoms:

Stage 1 (Early)

• Indigestion or a burning sensation (heartburn)
• Loss of appetite, especially for meat
• Abdominal discomfort or irritation

Stage 2 (Middle)

• Weakness and fatigue
• Bloating of the stomach, usually after meals

Stage 3 (Late)

• Abdominal pain in the upper abdomen
• Nausea and occasional vomiting
• Diarrhea or constipation
• Weight loss
• Bleeding (vomiting blood or having blood in the stool) which will appear as black. This can lead to anemia.
• Dysphagia; this feature suggests a tumor in the cardia or extension of the gastric tumor in to the esophagus.

Note that these can be symptoms of other problems such as a stomach virus, gastric ulcer or tropical sprue.

Causes

Infection by Helicobacter pylori is believed to be the cause of most stomach cancer while autoimmune atrophic gastritis, intestinal metaplasia and various genetic factors are associated with increased risk levels. The Merck Manual states that diet plays no role in the genesis of stomach cancer.^[2] However, the American Cancer Society lists the following dietary risks, and protective factors, for stomach cancer: "smoked foods, salted fish and meat, and pickled vegetables (appear to increase the risk of stomach cancer.) Nitrates and nitrites are substances commonly found in cured meats. They can be converted by certain bacteria, such as H. pylori, into compounds that have been found to cause stomach cancer in animals. On the other hand, eating fresh fruits and vegetables that contain antioxidant vitamins (such as A and C) appears to lower the risk of stomach cancer."^[3] A December 2009 article in American Journal of Clinical Nutrition found a statistically significant inverse correlation between higher adherence to a Mediterranean Dietary Pattern and stomach cancer.^[4]

In more detail, H. pylori is the main risk factor in 65–80% of gastric cancers, but in only 2% of such infections.^[5] Approximately ten percent of cases show a genetic component.^[6] Some studies indicate that bracken consumption and spores are correlated with incidence of stomach cancer, though causality has yet to be established.^[7]

A very important but preventable cause of gastric cancer is tobacco smoking. Smoking increases the risk of developing gastric cancer considerably; from 40% increased risk for current smokers to 82% increase for heavy smokers which is nearly twice the risk for non-smoking population. Gastric cancers due to smoking mostly occur in upper part of stomach near esophagus^[8][3][9] Another lifestyle cause of gastric cancer besides smoking is consumption of alcohol.^[10][11][12] Alcohol as cause of cancer along with tobacco smoking as cause of cancer increase the risk of developing other cancers as well.

Gastric cancer shows a male predominance in its incidence as up to three males are affected for every female. Estrogen may protect women against the development of this cancer form.^[13] A very small percentage of diffuse-type gastric cancers (see Histopathology below) are thought to be genetic. Hereditary Diffuse Gastric Cancer (HDGC) has recently been identified and research is ongoing. However, genetic testing and treatment options are already available for families at risk.^[14]

Some researchers^{[15][16][17][18][19][20]} showed a correlation between Iodine deficiency or excess, iodine-deficient goitre and gastric cancer; a decrease of the incidence of death rate from stomach cancer after implementation of the effective I-prophylaxis was reported too.^[21] The proposed mechanism of action is that iodide ion can function in gastric mucosa as an antioxidant reducing species that can detoxify poisonous reactive oxygen species, such as hydrogen peroxide.

The International Cancer Genome Consortium is leading efforts to map stomach cancer's complete genome.^{[citation needed]}

Diagnosis

To find the cause of symptoms, the doctor asks about the patient's medical history, does a physical exam, and may order laboratory studies. The patient may also have one or all of the following exams:

• Gastroscopic exam is the diagnostic method of choice. This involves insertion of a fiber optic camera into the stomach to visualize it.
• Upper GI series (may be called barium roentgenogram)
• Computed tomography or CT scanning of the abdomen may reveal gastric cancer, but is more useful to determine invasion into adjacent tissues, or the presence of spread to local lymph nodes.

Abnormal tissue seen in a gastroscope examination will be 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 increased yield of detect mucosa with a dye that accentuates the cell structure and can identify areas of dysplasia. Endocytoscopy involves ultra-high magnification to visualize cellular structure to better determine areas of dysplasia. Other gastroscopic modalities such as optical coherence tomography are also being tested investigationally for similar applications.^[22]

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 sign of Leser-Trelat, which is the rapid development of skin lesions known as seborrheic keratoses.^[23]

Various blood tests may be done; including: Complete Blood Count (CBC) to check for anemia. Also, a stool test may be performed to check for blood in the stool.

Histopathology

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.

• Gastric adenocarcinoma is a malignant epithelial tumor, originating from glandular epithelium of the gastric mucosa. Stomach cancers are overwhelmingly adenocarcinomas (90%).^[24] 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 thence the muscularis propria. Intestinal type adenocarcinoma tumor cells describe irregular tubular structures, harboring pluristratification, multiple lumens, reduced stroma ("back to back" aspect). Often, it associates intestinal metaplasia in neighboring 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, leather-bottle stomach) Tumor 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. If the mucus remains inside the tumor cell, it pushes the nucleus to the periphery- "signet-ring cell".
• Around 5% of gastric malignancies are lymphomas (MALTomas, or MALT lymphoma).^[25]
• Carcinoid and stromal tumors may also occur.

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, the pancreas, and other organs near the stomach as well as to the lungs, the doctor may order a CT scan, a PET scan, an endoscopic ultrasound exam, or other tests to check these areas. Blood tests for tumor markers, such as carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 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:^[26][27]

• Stage 0. Limited to the inner lining of the stomach. Treatable by endoscopic mucosal resection when found very early (in routine screenings); 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. 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. 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 metastatized 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.

The TNM staging system is also used.^[28]

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.^[29] A Minnesota population was diagnosed 10% in Stage I, 13% in Stage II, and 18% in Stage III.^[30] 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.^[31]

Management

As with any cancer, treatment is adapted to fit each person's individual needs and depends on the size, location, and extent of the tumor, the stage of the disease, and general health. Cancer of the stomach is difficult to cure unless it is found in 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, and/or radiation therapy. New treatment approaches such as biological therapy and improved ways of using current methods are being studied in clinical trials.^{[citation needed]} An antibody-drug conjugate IMGN242 is in phase II clinical trials.^[32][33] There is a well known remedy that eating jalapeño peppers daily can help reduce the pain of stomach cancer. Some think this is because it reduces the gastric acid in your stomach and helps numb the stomach walls.^{[citation needed]}

Surgery

Surgery is the most common treatment. The surgeon removes part or all of the stomach, as well as the surrounding lymph nodes, with the basic goal of removing all cancer and a margin of normal tissue. Depending on the extent of invasion and the location of the tumor, surgery may also include removal of part of the intestine or pancreas. Tumors in the lower part of the stomach may call for a Billroth I or Billroth II procedure.

Endoscopic mucosal resection (EMR)^[34] is a treatment for early gastric cancer (tumor only involves the mucosa) that has been pioneered in Japan, but is also available in the United States at some centers. In this procedure, 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 (ESD) 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.

Surgical interventions are currently curative in less than 40% of cases, and, in cases of metastasis, may only be palliative.

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: 5-FU (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. The relative benefits of these different drugs, alone and in combination, are unclear.^[35] Clinical researchers have explored the benefits of giving chemotherapy before surgery to shrink the tumor, or as adjuvant therapy after surgery to destroy remaining cancer cells. Combination treatment with chemotherapy and radiation therapy has some activity in selected post surgical settings. For patients who have HER2 overexpressing metastatic gastric or gastroesophageal (GE) junction adenocarcinoma, who have not received prior treatment for their metastatic disease, the US Food and Drug Administration granted approval (2010 October) for trastuzumab (Herceptin, Genentech, Inc.) in combination with cisplatin and a fluoropyrimidine (capecitabine or 5-fluorouracil). This was based on an improvement of the median overall survival (OS) of 2.5 months^[36] with trastuzumab plus chemotherapy treatment compared to chemotherapy alone (BO18255 ToGA trial). The combination of Herceptin with chemotherapy for treating metastatic gastric cancer was also sanctioned by the European regulatory authorities (2010 January). Doctors have also tested putting the anticancer drugs directly into the abdomen, often with warmed solutions of the medication (intraperitoneal hyperthermic chemoperfusion).^[37]

Radiation

Radiation therapy (also called radiotherapy) is the use of high-energy rays to damage cancer cells and stop them from growing. When used, it is generally in combination with surgery and chemotherapy, or used only with chemotherapy in cases where the individual is unable to undergo surgery. Radiation therapy may be used to relieve pain or blockage by shrinking the tumor for palliation of incurable disease.

Multimodality therapy

While previous studies of multimodality therapy (combinations of surgery, chemotherapy and radiation therapy) gave mixed results, the Intergroup 0116 (SWOG 9008) study^[38] showed a survival benefit to the combination of chemotherapy and radiation therapy in patients with nonmetastatic, completely resected gastric cancer. Patients were randomized after surgery to the standard group of observation alone, or the study arm of combination chemotherapy and radiation therapy. Those in the study arm receiving chemotherapy and radiation therapy survived on average 36 months; compared to 27 months with observation.

Epidemiology

Age-standardized death from stomach cancer per 100,000 inhabitants in 2004.^[39]

no data   <3.5   3.5-8   8-12.5   12.5-17   17-21.5   21.5-26

26-30.5   30.5-35   35-40   40-45   45-50   >50

Stomach cancer is the fourth most common cancer worldwide with 930,000 cases diagnosed in 2002.^[40] It is a disease with a high death rate (~800,000 per year) making it the second most common cause of cancer death worldwide after lung cancer.^[1] It is more common in men and in developing countries.^[40][41]

It represents roughly 2% (25,500 cases) of all new cancer cases yearly in the United States, but it is more common in other countries. It is the leading cancer type in Korea, with 20.8% of malignant neoplasms.

Metastasis occurs in 80-90% of individuals with stomach cancer, with a six month survival rate of 65% in those diagnosed in early stages and less than 15% of those diagnosed in late stages.

One in 50 patients of all ages who seek medical attention for burping and indigestion are diagnosed with stomach cancer.^[42] Out of 10 million people in the Czech Republic, only 3 new cases of stomach cancer in people under 30 years of age in 1999 were diagnosed.^[43] Other studies show that 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.^[44]

For Taiwan (statistic not shown on the above map), the mortality was 11.75 per 100,000 (1996).

In 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. In order to determine whether cancer is present in the stomach, special X-rays and/or abdominal ultrasound may be performed. Gastroscopy, a test using an instrument called 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.^[45] 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

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External links

Wikimedia Commons has media related to: Stomach cancer

• National Cancer Institute Gastric cancer treatment guidelines
• GeneReview/NIH/UW entry on Hereditary Diffuse Gastric Cancer
• Gastric Cancer Surgery

v d e Tumors: digestive system neoplasia (C15–C26/D12–D13, 150–159/211) GI tract Upper GI tract Esophagus Squamous cell carcinoma · Adenocarcinoma Stomach Gastric carcinoma · Signet ring cell carcinoma · Gastric lymphoma (MALT lymphoma) · Linitis plastica Lower GI tract Small intestine Duodenal cancer (Adenocarcinoma) Appendix Carcinoid · Pseudomyxoma peritonei Colon/rectum colorectal polyp: Peutz-Jeghers syndrome · Juvenile polyposis syndrome · Familial adenomatous polyposis/Gardner's syndrome · Cronkhite–Canada syndrome neoplasm: Adenocarcinoma · Familial adenomatous polyposis · Hereditary nonpolyposis colorectal cancer Anus Squamous cell carcinoma Upper and/or lower Gastrointestinal stromal tumor · Krukenberg tumor (metastatic) Accessory Liver malignant: Hepatocellular carcinoma (Fibrolamellar) · Hepatoblastoma benign: Hepatocellular adenoma · Cavernous hemangioma hyperplasia: Focal nodular hyperplasia · Nodular regenerative hyperplasia Biliary tract bile duct: Cholangiocarcinoma · Klatskin tumor gallbladder: Gallbladder cancer Pancreas exocrine pancreas: Adenocarcinoma · Pancreatic ductal carcinoma cystic neoplasms: Serous microcystic adenoma · Intraductal papillary mucinous neoplasm · Mucinous cystic neoplasm · Solid pseudopapillary neoplasm Pancreatoblastoma Peritoneum Primary peritoneal carcinoma · Peritoneal mesothelioma · Desmoplastic small round cell tumor M: DIG anat(t, g, p)/phys/devp/enzy noco/cong/tumr, sysi/epon proc, drug(A2A/2B/3/4/5/6/7/14/16), blte

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