Stomach Cancer

*Stomach cancer facts medical author: Charles P. Davis, MD, PhD

• The stomach is a hollow organ that liquefies food and is part of the digestive system.
• Cancer is the growth of abnormal (malignant) body cells: stomach cancer cells spread by breaking away from other cancer cells and go into the bloodstream or lymphatics while others penetrate into organs near the stomach.
• Although the cause of stomach cancer development is not known, risk factors include inflammation of the stomach, Helicobacter pylori infection, smoking, poor diet, obesity, lack of physical activity, and the history of stomach cancer in the family.
• The symptoms of stomach cancer may include discomfort and/or pain in the stomach, nausea and vomiting, weight loss, difficulty swallowing, vomiting blood, blood in the stool, and feeling full or bloated after a small meal.
• Stomach cancer is diagnosed by a physical exam, medical history, endoscopy, and biopsy of the tissue.
• Stomach cancer is staged according to where the cancers found and how far it has invaded the stomach tissue, or if it has spread beyond the stomach and into other organs (stages 0 to IV).
• The treatment of stomach cancer depends on the size and location of the tumor, the stage of the disease and the patient's general health.
• Surgery is done to remove cancer tissue; in general, two procedures are common: partial (subtotal) gastrectomy and total gastrectomy.
• Chemotherapy is the use of drugs to kill cancer cells: it may be used before or after surgery.
• Radiation therapy uses high-energy rays to kill cancer cells: it is used frequently along with chemotherapy.
• Many doctors recommend getting a second opinion before starting treatment: this article provides contact phone numbers to several institutions that can help find a doctor to give a second opinion.
• Good nutrition after stomach surgery may require supplements like vitamins and minerals, plus changing your eating habits.
• Surgery, a stent placement, radiation therapy, and laser therapy are treatment options for cancers that block the gastrointestinal (GI) tract.
• Tests to rule out recurrence of cancer; complementary and alternative medicine should be discussed with you doctor.
• There are support groups for cancer patients; contact information is listed.
• Contact information for joining clinical trials is also included in this article.

The stomach is a J-shaped organ in the upper abdomen. It is part of the digestive system, which processes nutrients (vitamins, minerals, carbohydrates, fats, proteins, and water) in foods that are eaten and helps pass waste material out of the body. Food moves from the throat to the stomach through a hollow, muscular tube called the esophagus. After leaving the stomach, partly-digested food passes into the small intestine and then into the large intestine.

The wall of the stomach is made up of 3 layers of tissue: the mucosal (innermost) layer, the muscularis (middle) layer, and the serosal (outermost) layer. Gastric cancer begins in the cells lining the mucosal layer and spreads through the outer layers as it grows.

Stromal tumors of the stomach begin in supporting connective tissue and are treated differently from gastric cancer.

Anything that increases your risk of getting a disease is called a risk factor. Having a risk factor does not mean that you will get cancer; not having risk factors doesn't mean that you will not get cancer. Talk with your doctor if you think you may be at risk. Risk factors for gastric cancer include the following:

• Having any of the following medical conditions:
  • Helicobacter pylori (H. pylori) infection of the stomach.
  • Chronic gastritis (inflammation of the stomach).
  • Pernicious anemia.
  • Intestinal metaplasia (a condition in which the normal stomach lining is replaced with the cells that line the intestines).
  • Familial adenomatous polyposis (FAP) or gastric polyps.
• Eating a diet high in salted, smoked foods and low in fruits and vegetables.
• Eating foods that have not been prepared or stored properly.
• Being older or male.
• Smoking cigarettes.
• Having a mother, father, sister, or brother who has had stomach cancer.

These and other signs and symptoms may be caused by gastric cancer or by other conditions.

In the early stages of gastric cancer, the following symptoms may occur:

• Indigestion and stomach discomfort.
• A bloated feeling after eating.
• Mild nausea.
• Loss of appetite.
• Heartburn.

In more advanced stages of gastric cancer, the following signs and symptoms may occur:

• Blood in the stool.
• Vomiting.
• Weight loss for no known reason.
• Stomach pain.
• Jaundice (yellowing of eyes and skin).
• Ascites (build-up of fluid in the abdomen).
• Trouble swallowing.

Check with your doctor if you have any of these problems.

The following tests and procedures may be used:

• Physical exam and history: An exam of the body to check general signs of health, including checking for signs of disease, such as lumps or anything else that seems unusual. A history of the patient's health habits and past illnesses and treatments will also be taken.
• Blood chemistry studies: A procedure in which a blood sample is checked to measure the amounts of certain substances released into the blood by organs and tissues in the body. An unusual (higher or lower than normal) amount of a substance can be a sign of disease.
• Complete blood count (CBC): A procedure in which a sample of blood is drawn and checked for the following:
  • The number of red blood cells, white blood cells, and platelets.
  • The amount of hemoglobin (the protein that carries oxygen) in the red blood cells.
  • The portion of the sample made up of red blood cells.
• Upper endoscopy: A procedure to look inside the esophagus, stomach, and duodenum (first part of the small intestine) to check for abnormal areas. An endoscope (a thin, lighted tube) is passed through the mouth and down the throat into the esophagus.
• Barium swallow: A series of x-rays of the esophagus and stomach. The patient drinks a liquid that contains barium (a silver-white metallic compound). The liquid coats the esophagus and stomach, and x-rays are taken. This procedure is also called an upper GI series.
• CT scan (CAT scan): A procedure that makes a series of detailed pictures of areas inside the body, taken from different angles. The pictures are made by a computer linked to an x-ray machine. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography.
• Biopsy: The removal of cells or tissues so they can be viewed under a microscope to check for signs of cancer. A biopsy of the stomach is usually done during the endoscopy.

The sample of tissue may be checked to measure how many HER2 genes there are and how much HER2 protein is being made. If there are more HER2 genes or higher levels of HER2 protein than normal, the cancer is called HER2 positive. HER2-positive gastric cancer may be treated with a monoclonal antibody that targets the HER2 protein.

The prognosis (chance of recovery) and treatment options depend on the following:

• The stage of the cancer (whether it is in the stomach only or has spread to lymph nodes or other places in the body).
• The patient's general health.

When gastric cancer is found very early, there is a better chance of recovery. Gastric cancer is often in an advanced stage when it is diagnosed. At later stages, gastric cancer can be treated but rarely can be cured. Taking part in one of the clinical trials being done to improve treatment should be considered.

The process used to find out if cancer has spread within the stomach or to other parts of the body is called staging. The information gathered from the staging process determines the stage of the disease. It is important to know the stage in order to plan treatment.

The following tests and procedures may be used in the staging process:

• CEA (carcinoembryonic antigen) assay: Tests that measure the level of CEA in the blood. This substance is released into the bloodstream from both cancer cells and normal cells. When found in higher than normal amounts, it can be a sign of gastric cancer or other conditions.
• Endoscopic ultrasound (EUS): A procedure in which an endoscope is inserted into the body, usually through the mouth or rectum. An endoscope is a thin, tube-like instrument with a light and a lens for viewing. A probe at the end of the endoscope is used to bounce high-energy sound waves (ultrasound) off internal tissues or organs and make echoes. The echoes form a picture of body tissues called a sonogram. This procedure is also called endosonography.
• CT scan (CAT scan): A procedure that makes a series of detailed pictures of areas inside the body, taken from different angles. The pictures are made by a computer linked to an x-ray machine. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography.
• PET scan (positron emission tomography scan): A procedure to find malignant tumor cells in the body. A small amount of radioactive glucose (sugar) is injected into a vein. The PET scanner rotates around the body and makes a picture of where glucose is being used in the body. Malignant tumor cells show up brighter in the picture because they are more active and take up more glucose than normal cells do. A PET scan and CT scan may be done at the same time. This is called a PET-CT.

Cancer can spread through tissue, the lymph system, and the blood:

• Tissue. The cancer spreads from where it began by growing into nearby areas.
• Lymph system. The cancer spreads from where it began by getting into the lymph system. The cancer travels through the lymph vessels to other parts of the body.
• Blood. The cancer spreads from where it began by getting into the blood. The cancer travels through the blood vessels to other parts of the body.

When cancer spreads to another part of the body, it is called metastasis. Cancer cells break away from where they began (the primary tumor) and travel through the lymph system or blood.

• Lymph system. The cancer gets into the lymph system, travels through the lymph vessels, and forms a tumor (metastatic tumor) in another part of the body.
• Blood. The cancer gets into the blood, travels through the blood vessels, and forms a tumor (metastatic tumor) in another part of the body.

The metastatic tumor is the same type of cancer as the primary tumor. For example, if gastric cancer spreads to the liver, the cancer cells in the liver are actually gastric cancer cells. The disease is metastatic gastric cancer, not liver cancer.

Stage 0 (Carcinoma in Situ)

In stage 0, abnormal cells are found in the inside lining of the mucosa (innermost layer) of the stomach wall. These abnormal cells may become cancer and spread into nearby normal tissue. Stage 0 is also called carcinoma in situ.

Stage I

In stage I, cancer has formed in the inside lining of the mucosa (innermost layer) of the stomach wall. Stage I is divided into stage IA and stage IB, depending on where the cancer has spread.

• Stage IA: Cancer may have spread into the submucosa (layer of tissue next to the mucosa) of the stomach wall.
• Stage IB: Cancer:
  • may have spread into the submucosa (layer of tissue next to the mucosa) of the stomach wall and is found in 1 or 2 lymph nodes near the tumor; or
  • has spread to the muscle layer of the stomach wall.

Stage II

Stage II gastric cancer is divided into stage IIA and stage IIB, depending on where the cancer has spread.

• Stage IIA: Cancer:
  • has spread to the subserosa (layer of tissue next to the serosa) of the stomach wall; or
  • has spread to the muscle layer of the stomach wall and is found in 1 or 2 lymph nodes near the tumor; or
  • may have spread to the submucosa (layer of tissue next to the mucosa) of the stomach wall and is found in 3 to 6 lymph nodes near the tumor.
• Stage IIB: Cancer:
  • has spread to the serosa (outermost layer) of the stomach wall; or
  • has spread to the subserosa (layer of tissue next to the serosa) of the stomach wall and is found in 1 or 2 lymph nodes near the tumor; or
  • has spread to the muscle layer of the stomach wall and is found in 3 to 6 lymph nodes near the tumor; or
  • may have spread to the submucosa (layer of tissue next to the mucosa) of the stomach wall and is found in 7 or more lymph nodes near the tumor.

Stage III

Stage III gastric cancer is divided into stage IIIA, stage IIIB, and stage IIIC, depending on where the cancer has spread.

• Stage IIIA: Cancer has spread to:
  • the serosa (outermost) layer of the stomach wall and is found in 1 or 2 lymph nodes near the tumor; or
  • the subserosa (layer of tissue next to the serosa) of the stomach wall and is found in 3 to 6 lymph nodes near the tumor; or
  • the muscle layer of the stomach wall and is found in 7 or more lymph nodes near the tumor.
• Stage IIIB: Cancer has spread to:
  • nearby organs such as the spleen, transverse colon, liver, diaphragm, pancreas, kidney, adrenal gland, or small intestine, and may be found in 1 or 2 lymph nodes near the tumor; or
  • the serosa (outermost layer) of the stomach wall and is found in 3 to 6 lymph nodes near the tumor; or
  • the subserosa (layer of tissue next to the serosa) of the stomach wall and is found in 7 or more lymph nodes near the tumor.
• Stage IIIC: Cancer has spread to:
  • nearby organs such as the spleen, transverse colon, liver, diaphragm, pancreas, kidney, adrenal gland, or small intestine, and may be found in 3 or more lymph nodes near the tumor; or
  • the serosa (outermost layer) of the stomach wall and is found in 7 or more lymph nodes near the tumor.

Stage IV

In stage IV, cancer has spread to distant parts of the body.

Recurrent gastric cancer is cancer that has recurred (come back) after it has been treated. The cancer may come back in the stomach or in other parts of the body such as the liver or lymph nodes.

Different types of treatments are available for patients with gastric cancer. Some treatments are standard (the currently used treatment), and some are being tested in clinical trials. A treatment clinical trial is a research study meant to help improve current treatments or obtain information on new treatments for patients with cancer. When clinical trials show that a new treatment is better than the standard treatment, the new treatment may become the standard treatment. Patients may want to think about taking part in a clinical trial. Some clinical trials are open only to patients who have not started treatment.

Five types of standard treatment are used:

Surgery

Surgery is a common treatment of all stages of gastric cancer. The following types of surgery may be used:

• Subtotal gastrectomy: Removal of the part of the stomach that contains cancer, nearby lymph nodes, and parts of other tissues and organs near the tumor. The spleen may be removed. The spleen is an organ in the upper abdomen that filters the blood and removes old blood cells.
• Total gastrectomy: Removal of the entire stomach, nearby lymph nodes, and parts of the esophagus, small intestine, and other tissues near the tumor. The spleen may be removed. The esophagus is connected to the small intestine so the patient can continue to eat and swallow.

If the tumor is blocking the stomach but the cancer cannot be completely removed by standard surgery, the following procedures may be used:

• Endoluminal stent placement: A procedure to insert a stent (a thin, expandable tube) in order to keep a passage (such as arteries or the esophagus) open. For tumors blocking the passage into or out of the stomach, surgery may be done to place a stent from the esophagus to the stomach or from the stomach to the small intestine to allow the patient to eat normally.
• Endoluminal laser therapy: A procedure in which an endoscope (a thin, lighted tube) with a laser attached is inserted into the body. A laser is an intense beam of light that can be used as a knife.
• Gastrojejunostomy: Surgery to remove the part of the stomach with cancer that is blocking the opening into the small intestine. The stomach is connected to the jejunum (a part of the small intestine) to allow food and medicine to pass from the stomach into the small intestine.

Chemotherapy

Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. When chemotherapy is taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can reach cancer cells throughout the body (systemic chemotherapy). When chemotherapy is placed directly into the cerebrospinal fluid, an organ, or a body cavity such as the abdomen, the drugs mainly affect cancer cells in those areas (regional chemotherapy). The way the chemotherapy is given depends on the type and stage of the cancer being treated.

Radiation therapy

Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells or keep them from growing. There are two types of radiation therapy:

• External radiation therapy uses a machine outside the body to send radiation toward the cancer.
• Internal radiation therapy uses a radioactive substance sealed in needles, seeds, wires, or catheters that are placed directly into or near the cancer.

The way the radiation therapy is given depends on the type and stage of the cancer being treated. External radiation therapy is used to treat gastric cancer.

Chemoradiation

Chemoradiation therapy combines chemotherapy and radiation therapy to increase the effects of both. Chemoradiation given after surgery, to lower the risk that the cancer will come back, is called adjuvant therapy. Chemoradiation given before surgery, to shrink the tumor (neoadjuvant therapy), is being studied.

Targeted therapy

Targeted therapy is a type of treatment that uses drugs or other substances to identify and attack specific cancer cells without harming normal cells. Monoclonal antibody therapy is a type of targeted therapy used in the treatment of gastric cancer.

Monoclonal antibody therapy uses antibodies made in the laboratory from a single type of immune system cell. These antibodies can identify substances on cancer cells or normal substances that may help cancer cells grow. The antibodies attach to the substances and kill the cancer cells, block their growth, or keep them from spreading. Monoclonal antibodies are given by infusion. They may be used alone or to carry drugs, toxins, or radioactive material directly to cancer cells. For stage IV gastric cancer and gastric cancer that has recurred, monoclonal antibodies, such as trastuzumab or ramucirumab, may be given. Trastuzumab blocks the effect of the growth factor protein HER2, which sends growth signals to gastric cancer cells. Ramucirumab blocks the effect of the protein VEGF and may prevent the growth of new blood vessels that tumors need to grow.

For some patients, taking part in a clinical trial may be the best treatment choice. Clinical trials are part of the cancer research process. Clinical trials are done to find out if new cancer treatments are safe and effective or better than the standard treatment.

Many of today's standard treatments for cancer are based on earlier clinical trials. Patients who take part in a clinical trial may receive the standard treatment or be among the first to receive a new treatment.

Patients who take part in clinical trials also help improve the way cancer will be treated in the future. Even when clinical trials do not lead to effective new treatments, they often answer important questions and help move research forward.

Some clinical trials only include patients who have not yet received treatment. Other trials test treatments for patients whose cancer has not gotten better. There are also clinical trials that test new ways to stop cancer from recurring (coming back) or reduce the side effects of cancer treatment.

Clinical trials are taking place in many parts of the country.

Some of the tests that were done to diagnose the cancer or to find out the stage of the cancer may be repeated. Some tests will be repeated in order to see how well the treatment is working. Decisions about whether to continue, change, or stop treatment may be based on the results of these tests.

Some of the tests will continue to be done from time to time after treatment has ended. The results of these tests can show if your condition has changed or if the cancer has recurred (come back). These tests are sometimes called follow-up tests or check-ups.

Stage 0 (Carcinoma in Situ)

Treatment of stage 0 is usually surgery (total or subtotal gastrectomy).

Stage I Gastric Cancer

Treatment of stage I gastric cancer may include the following:

• Surgery (total or subtotal gastrectomy).
• Surgery (total or subtotal gastrectomy) followed by chemoradiation therapy.
• A clinical trial of chemoradiation therapy given before surgery.

Stage II Gastric Cancer

Treatment of stage II gastric cancer may include the following:

• Surgery (total or subtotal gastrectomy).
• Surgery (total or subtotal gastrectomy) followed by chemoradiation therapy or chemotherapy.
• Chemotherapy given before and after surgery.
• A clinical trial of surgery followed by chemoradiation therapy testing new anticancer drugs.
• A clinical trial of chemoradiation therapy given before surgery.

Stage III Gastric Cancer

Treatment of stage III gastric cancer may include the following:

• Surgery (total gastrectomy).
• Surgery followed by chemoradiation therapy or chemotherapy.
• Chemotherapy given before and after surgery.
• A clinical trial of surgery followed by chemoradiation therapy testing new anticancer drugs.
• A clinical trial of chemoradiation therapy given before surgery.

Stage IV and Recurrent Gastric Cancer

Treatment of stage IV or recurrent gastric cancer may include the following:

• Chemotherapy as palliative therapy to relieve symptoms and improve the quality of life.
• Targeted therapy with a monoclonal antibody with or without chemotherapy.
• Endoluminal laser therapy or endoluminal stent placement to relieve a blockage in the stomach, or gastrojejunostomy to bypass the blockage.
• Radiation therapy as palliative therapy to stop bleeding, relieve pain, or shrink a tumor that is blocking the stomach.
• Surgery as palliative therapy to stop bleeding or shrink a tumor that is blocking the stomach.
• A clinical trial of new combinations of chemotherapy as palliative therapy to relieve symptoms and improve the quality of life.