Overview of Gastric Cancer

Diagnosing gastric cancer; know the risk factors, signs & symptoms, and how gastric cancer is evaluated by your doctor

Overview of Gastric Cancer

Medically reviewed by C.H. Weaver M.D. Medical Editor (08/2018)

The stomach is part of the digestive system. Food passes through the esophagus into the stomach at the level of the diaphragm, which is the breathing muscle that separates the abdomen from the chest. The stomach extends from the diaphragm to the duodenum, which is the first portion of the small intestine.

  • Signs & Symptoms of Gastric Cancer
  • Risk Factors for Gastric Cancer
  • Diagnosis & Tests
  • Staging of Gastric Cancer
  • Screening & Prevention of Gastric Cancer

Cancer of the stomach is called gastric cancer. Gastric adenocarcinoma is the most common cancer of the stomach and it arises from the cells (columnar epithelium) lining the surface of the stomach. The primary risk factor associated with gastric cancer is infection with the bacterium, Helicobacter pylori (H. pylori). H. pylori can be treated with antibiotics, which may reduce the risk of gastric cancer.[1]

There has been a marked decline in the incidence of gastric cancer in the United States and many other industrialized nations over the past 20-30 years. However, there has been an increase in cancers arising at the junction of the esophagus with the stomach. Approximately 21,000 new cases of gastric cancer are diagnosed in the United States each year, with approximately 10,500 yearly deaths from gastric cancer.[2]

Gastric cancer is more common and is a major cause of cancer-related death in Asian countries such as Korea, China, Taiwan and Japan. Thus, much of the knowledge about treatment, especially surgery, comes from these countries. The incidence of gastric cancer is so high in these countries that they perform routine screening by esophagoscopy for detection of early gastric cancer. Early detection programs, such as those implemented in Japan, are not practiced elsewhere in the world because of the lower incidence of gastric cancer. For this reason, gastric cancer is detected at a later stage (extent of spread) in the U.S. and Europe than in Japan.

Surgery is the primary treatment of gastric cancer. Two main factors affect outcome following surgery for gastric cancer, the depth of the penetration of the primary cancer into the wall of the stomach and the presence or absence of spread of cancer to regional or adjacent lymph nodes. The site of the primary cancer also influences outcome, as upper stomach cancers are associated with a worse outcome than cancers of the middle and lower stomach.

Symptoms & Signs of Gastric Cancer

Individuals with gastric cancer may experience the following symptoms or signs. Sometimes, people with gastric cancer do not have any of these changes, or the cause of a symptom may be another medical condition that is not cancer.

  • Indigestion or heartburn
  • Vomiting
  • Nausea
  • Pain or discomfort in the abdomen
  • Diarrhea or constipation
  • Bloating of the stomach after meals
  • Loss of appetite
  • Sensation of food getting stuck in the throat while eating

Symptoms of advanced stomach cancer may include:

  • Weakness and fatigue
  • Vomiting blood or having blood in the stool
  • Unexplained weight loss

Cause of Gastric Cancer

Gastric cancer begins when healthy cells acquire a genetic change (mutation) that causes them to turn into abnormal cells. Development of gastric cancer can occur as a result of chronic inflammation due to infection with the Helicobacter pylori bacteria.[1]

Risk Factors for Gastric Cancer

A risk factor is anything that increases a person’s chance of developing cancer. Risk factors can influence the development of cancer but most do not directly cause cancer. Many individuals with risk factors will never develop cancer and others with no known risk factors will. Most gastric cancers develop sporadically, which means for no known reason. Some gastric cancers however are more likely to develop in individuals with certain risk factors that increase an individuals chance of developing gastric cancer.

The following factors may raise a person’s risk for developing gastric cancer:[2]

  • Age. Stomach cancer occurs most commonly in people older than 55. Most people diagnosed with stomach cancer are in their 60s and 70s.
  • Gender. Men are twice as likely to develop stomach cancer as women.
  • Race/ethnicity. Stomach cancer is more common in black, Hispanic, and Asian people than in white people.
  • Tobacco. Using any form of tobacco: cigarettes, cigars, pipes, chewing tobacco, and snuff increases the risk of gastric cancer.
  • Alcohol. Heavy drinking over a long period of time increases the risk of developing gastric cancer
  • Obesity. Being severely overweight and having too much body fat can increase a person’s risk.
  • Bacteria. Helicobacter pylori, also called H. pylori, causes stomach inflammation and ulcers. It is also considered one of the primary causes of stomach cancer. Testing for H. pylori is available and an infection can be treated with antibiotics.[1]
  • Family history/genetics. People who have a parent, child, or sibling who has had gastric cancer are at increased risk. In addition, certain inherited genetic disorders may increase the risk of gastric cancer.
  • Hereditary diffuse gastric cancer
  • Lynch syndrome
  • Hereditary breast and ovarian cancer (HBOC)
  • Familial adenomatous polyposis (FAP)
  • Diet. Eating a diet high in salt has been linked to an increased risk of stomach cancer. This includes foods preserved by drying, smoking, salting, or pickling and foods high in added salt.
  • Previous surgery or health conditions. People who have had stomach surgery, pernicious anemia, or achlorhydria have a higher risk of stomach cancer.
  • Occupational exposure. Exposure to certain dusts and fumes may increase the risk of developing stomach cancer.

Diagnosis & Tests for Gastric Cancer

Doctors use many tests to find, or diagnose, cancer. They also do tests to learn if cancer has spread to another part of the body from where it started. A biopsy is the only certain way to confirm a diagnosis of gastric cancer. When performing a biopsy, the doctor takes a sample of tissue for testing in a laboratory. The doctor may recommend some or all of these tests to help make a diagnosis.

Genomic or Biomarker Testing-Precision Cancer Medicine

The purpose of precision cancer medicine is to define the genomic alterations in the cancers DNA that are driving that specific cancer. Precision cancer medicine utilizes molecular diagnostic and genomic testing including DNA sequencing, to identify cancer-driving abnormalities in a cancer’s genome. Once a genetic abnormality is identified, a specific targeted therapy can be designed to attack a specific mutation or other cancer-related change in the DNA programming of the cancer cells. Precision cancer medicine uses targeted drugs and immunotherapies engineered to directly attack the cancer cells with specific abnormalities, leaving normal cells largely unharmed.

By testing a cancer for specific unique biomarkers doctors can offer the most personalized treatment approach utilizing precision medicines. Human epidermal growth receptor 2 (HER2) is a specialized protein found on the surface of cells that can be targeted with precision cancer medicines.[3]

Staging of Gastric Cancer

It is important to determine how much the cancer has spread before initiating treatment in order to select the best treatment option. Of particular concern is the presence of cancer in lymph nodes, spread of cancer to distant sites or local extension of cancer into surrounding structures, all of which might make attempts to remove all of the cancer with surgery impossible. Unfortunately, in many cases the true extent of spread of gastric cancer can only be determined at the time of surgical resection. Frequently, more advanced cancer is found during surgery than was detected through diagnostic procedures. The following diagnostic procedures may be used in the evaluation of gastric cancer.

  • Barium swallow, (esophagram): The patient swallows a liquid containing barium and then a series of x-rays are taken. Barium coats the surface of the esophagus, making cancer or other unusual changes easier to see on the x-ray. If there is an abnormal looking area, an upper endoscopy and biopsy to find out if it is cancerous is typically performed.
  • Computed Tomography (CT) Scan: A CT scan is a technique for imaging body tissues and organs, during which X-ray transmissions are converted to detailed images, using a computer to synthesize X-ray data. A CT scan is conducted with a large machine positioned outside the body that can rotate to capture detailed images of the organs and tissues inside the body.
  • Magnetic Resonance Imaging (MRI): MRI uses a magnetic field rather than X-rays, and can often distinguish more accurately between healthy and diseased tissue than a CT. An MRI gives a better picture of cancer located near bone than does CT, does not use radiation, and provides pictures from various angles that enable doctors to construct a three-dimensional image of the cancer.
  • Positron emission tomography (PET): Positron emission tomography scanning is an advanced technique for imaging body tissues and organs. One characteristic of living tissue is the metabolism of sugar. Prior to a PET scan, a substance containing a type of sugar attached to a radioactive isotope (a molecule that emits radiation) is injected into the patient’s vein. The cancer cells “take up” the sugar and attached isotope, which emits positively charged, low energy radiation (positrons) that create the production of gamma rays that can be detected by the PET machine to produce a picture. If no gamma rays are detected in the scanned area, it is unlikely that the mass in question contains living cancer cells.
  • Upper endoscopy or esophagus-gastric-duodenoscopy (EGD): An upper endoscopy is an examination performed through an endoscope, which is a thin flexible tube with a light and camera. The endoscope is inserted through the mouth into the esophagus and allows the physician to visualize, photograph, and biopsy the suspicious areas for cancer.
  • Thoracoscopy: A thoracoscopy is another procedure performed through an endoscope to examine the chest in order to determine the extent of spread of cancer in the chest.
  • Bronchoscopy: The doctor passes a thin, flexible tube with a light on the end into the mouth or nose, down through the windpipe, and into the breathing passages of the lungs. A bronchoscopy may be performed if a patient’s tumor is located in the upper two-thirds of the esophagus to find out if the tumor is growing into the person’s airway.
  • Endosonography: Endosonography refers to an ultrasound test performed through an endoscope. Ultrasound tests utilize sound waves to detect different densities of tissue, including cancer. Endosonography can detect spread of cancer into various layers of the stomach, adjacent organs and lymph nodes better than CT scanning.
  • Gastroscopy: A gastroscopy is an examination performed through an endoscope, which is a flexible tube inserted through the esophagus that allows the physician to visualize, photograph and biopsy (sample) the cancer. All patients have a gastroscopy with a biopsy to determine the histology or appearance of the cancer under the microscope.
  • Laparoscopy: Laparoscopy is a procedure that involves the insertion of an endoscope through a small incision in the abdomen. Laparoscopy is an important tool for staging and has proven to be more reliable than CT scanning in detecting spread of cancer to the liver and the lining of the abdomen (peritoneum).

The current methods of clinical staging of patients with gastric cancer are not perfect and are constantly changing as new and more reliable tests are developed. At this point, the results of surgery are much more reliable in determining the extent of cancer spread than tests performed before surgery. In order to learn more about the most recent information available concerning the treatment of gastric cancer, click on the appropriate stage.[4]

Stage 0: Cancer in situ is cancer that is limited to the surface layer of cells lining the stomach, which is called the epithelium.

Stage IA: Cancer invades beneath the surface layer of cells, but not into the muscle wall and there is no lymph node or distant spread of cancer.

Stage IB: Cancer invades beneath the surface layer of cells, with spread to 1-2 lymph nodes, or invades into the muscle of the wall of the stomach without regional lymph node or distant spread of cancer.

Stage II: Cancer invades beneath the surface, with spread to 3 or more lymph nodes; into the muscle of the wall of the stomach, with spread to 1-6 lymph nodes; into the next-to-the-last layer of the stomach, with spread to no more than 2 lymph nodes; or into the outermost layer of the stomach but not to the lymph nodes.

Stage III: Cancer has spread to adjacent structures and/or regional lymph nodes.

Stage IIIA: Cancer invades the muscle of the wall of the stomach and 7 or more lymph nodes, the next-to-the-last layer of the stomach and 3-6 lymph nodes, or the outermost layer of the stomach (the serosa) and 1-2 lymph nodes.

Stage IIIB: Cancer invades the next-to-the-last layer of the stomach and 7 or more lymph nodes, the outermost layer of the stomach and 3-6 lymph nodes, or adjacent structures and few (1-2) or no lymph nodes.

Stage IIIC: Cancer involves the outermost layer of the stomach and 7 or more lymph nodes, or adjacent structures and 3 or more lymph nodes.

Stage IV: Cancer has spread to distant sites.

Recurrent Cancer: The cancer has returned after primary treatment.

Screening & Prevention for Gastric Cancer

Information about the prevention of cancer and the science of screening appropriate individuals at high risk of developing cancer is gaining interest. Physicians and individuals alike recognize that the best “treatment” of cancer is preventing its occurrence in the first place or detecting it early when it may be most treatable.

Gastric cancer is characterized by the presence of cancer cells in the tissues of the stomach, which is located in the upper abdomen. Worldwide, gastric cancer is the third leading cause of cancer death in men and the fifth leading cause of cancer death in women.[5]

The chance of an individual developing cancer depends on both genetic and non-genetic factors. A genetic factor is an inherited, unchangeable trait, while a non-genetic factor is a variable in a person’s environment, which can often be changed. Non-genetic factors may include diet, exercise, or exposure to other substances present in our surroundings. These non-genetic factors are often referred to as environmental factors. Some non-genetic factors play a role in facilitating the process of healthy cells turning cancerous (e.g. the correlation between smoking and lung cancer) while other cancers have no known environmental correlation but are known to have a genetic predisposition. A genetic predisposition means that a person may be at higher risk for a certain cancer if a family member has that type of cancer.

Heredity or Genetic Factors

Researchers are beginning to identify genetic factors that contribute to the development of gastric cancer in some individuals. Specifically, the E-cadherin gene (CDH1) has been associated with a high risk of gastric cancer. Hereditary diffuse gastric cancer is a rare and deadly form of gastric cancer that can result from CDH1 mutations. Parents who carry this genetic mutation have a 50% chance of passing it along to their offspring. Three out of four people who inherit this genetic mutation will eventually develop gastric cancer.

Environmental or Non-Genetic Factors

Several risk factors have been associated with an increased risk of developing gastric cancer. These include infection with the Helicobacter pylori (H. pylori) bacterium, smoking, high consumption of smoked or salted foods, and low intake of fruits and vegetables. In addition, poor drinking water and a lack of refrigeration appear to contribute to the development of gastric cancer.

H. Pylori: The primary risk factor associated with gastric cancer is infection with the bacterium, Helicobacter pylori (H. pylori). H. pylori infection is common, but most people who are infected do not develop gastric cancer. The bacterium may be spread from person to person as well as through contact with contaminated food or water. Infection with H. pylori causes a reduction in the normal acid production and a shrinkage and loss of cells (called atrophy) in the stomach. Atrophy of the stomach is considered to be a precancerous condition. It can take decades for the precancerous conditions caused by H. pylori infection to develop into cancer. Individuals who live in regions that have high gastric cancer rates are often plagued with H. pylori stomach infections that develop early in life.

Prevention of Gastric Cancer

Two-thirds of cancer deaths in the U.S. can be linked to tobacco use, poor diet, obesity and lack of exercise. All of these factors can be modified. Nevertheless, an awareness of the opportunity to prevent cancer through changes in lifestyle is still under-appreciated.

Treatment of H. pylori infection: According to studies conducted in parts of the world where gastric cancer is common, treatment of H. pylori infections may reduce the risk of gastric cancer. In a large combined analysis of people infected with H. pylori, gastric cancer developed in 1.1% of those who received treatment to eradicate the infection and 1.7% of those who did not receive treatment.[3]

Aspirin: Aspirin is a type of non-steroid anti-inflammatory drug (NSAID). Studies have suggested that regular use of aspirin—but not other types of NSAIDs—may reduce the risk of gastric cancer.[6] Because regular aspirin use also carries some risks, however, people who are considering taking aspirin on a regular basis are advised to talk with their physician.

Diet: Diet is a fertile area for immediate individual and societal intervention to decrease the risk of developing certain cancers. Numerous studies have provided a wealth of often-contradictory information about the detrimental and protective factors of different foods.

In the case of gastric cancer, risk appears to be increased by high consumption of smoked, salted, or pickled foods, and decreased by regular consumption of fresh fruits and vegetables.[7]

Avoid tobacco smoke: Smoking increases the risk of many types of cancer, including gastric cancer. Never smoking (or quitting if you’ve started) provides many health benefits.

Screening and Early Detection of Gastric Cancer

For many types of cancer, progress in the areas of cancer screening and treatment has offered promise for earlier detection and higher cure rates. The term screening refers to the regular use of certain examinations or tests in persons who do not have any symptoms of a cancer but are at high risk for that cancer. When individuals are at high risk for a type of cancer, this means that they have certain characteristics or exposures, called risk factors that make them more likely to develop that type of cancer than those who do not have these risk factors. The risk factors are different for different types of cancer. An awareness of these risk factors is important because 1) some risk factors can be changed (such as smoking or dietary intake), thus decreasing the risk for developing the associated cancer; and 2) persons who are at high risk for developing a cancer can often undergo regular screening measures that are recommended for that cancer type. Researchers continue to study which characteristics or exposures are associated with an increased risk for various cancers, allowing for the use of more effective prevention, early detection and treatment strategies.

Gastric cancer rates have been steadily declining in the United States and at this point, routine screening for this cancer is not performed. Mass screening programs for gastric cancer have been most effective in high-risk areas, such as Japan. Early gastric cancer has a high cure rate when it is surgically removed. In some Japanese studies, as many as 40% of newly diagnosed patients have early gastric cancer and as many as 60% of patients are actively participating in mass screening programs. Routine screening in Japan involves gastroscopy.

Gastroscopy: A gastroscopy is an examination performed through an endoscope, which is a flexible tube inserted through the esophagus that allows the physician to visualize, photograph and biopsy (sample) the cancer.

References:

[1] American Cancer Society. Cancer Facts & Figures 2017.

[2] cancer.net/cancer-types/stomach-cancer/symptoms-and-signs

[3] Fuccio L, Zagari RM, Eusebi LH et al. Meta-analysis: can Helicobacter pylori eradication treatment reduce the risk for gastric cancer? Annals of Internal Medicine. 2009;151:121-8.

[4] AJCC Cancer Staging Manual, Seventh Edition.

[5] American Cancer Society. Global Cancer Facts & Figures, 2nd Edition. 2015.

[6] Epplein M, Nomura AMY, Wilkens LR, Henderson BE, Kolonel LN. Nonsteroidal anti-inflammatory drugs and risk of gastric adenocarcinoma: The Multiethnic Cohort Study. American Journal of Epidemiology. 2009; 170:507-14.

[7] National Cancer Institute. Gastric Cancer Treatment (PDQ®). Patient Version. Accessed June 20, 2017.

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