All About Gastric Cancer

Author: OncoLink Team
Content Contributor: Ryan P. Smith, MD, Eric Shinohara, MD, MSCI and Elizabeth Prechtel-Dunphy, MSN, CRNP, AOCN
Last Reviewed: April 26, 2019

What is the stomach?

The stomach is the muscular organ that holds and stores food. It is located just underneath the lower portion of the rib cage on the left side. It is connected to the mouth and throat by the esophagus. Using motion and acid, the stomach helps to partially digest food. The partially digested food is then emptied into the small intestine. The small intestine helps to absorb nutrients from the partially digested food.

What is gastric cancer?

Gastric cancer, or stomach cancer, is cancer of the stomach. Gastric cancer occurs when cells in the lining of the stomach grow uncontrollably and form tumors that can invade normal tissues and spread to other parts of the body.

Cancers are described by the types of cells from which they arise. About 90-95% of gastric cancers arise from the lining of the stomach, called adenocarcinoma. There are other cancers that can arise in the stomach, including gastrointestinal stromal tumors, lymphoma and carcinoid tumors, among others. 

Am I at risk for gastric cancer?

Each year, about 27,510 new cases of gastric cancer are diagnosed. The average age at diagnosis is 68 and its more common in men than women. The incidence of stomach cancer has drastically decreased since the 1930s. Although it is presumed that this is due to some sort of dietary or environmental factor(s), the exact reason behind this decrease is not known. One theory is that the advent of refrigeration led to decreased use of nitrites, "smoking" of foods, and other such forms of food preservation. 

Diets that consist of heavily salted, smoked, or pickled foods are associated with an increased risk of disease, while diets rich in fruits, vegetables, and dietary fiber are associated with a decreased risk of gastric cancer. Tobacco use has also been associated with an increase in gastric cancers. Heavy alcohol use may also be associated with a higher risk of gastric cancer.

There does appear to be a genetic link in some cases of gastric cancer. There are some genetic diseases such as Lynch syndrome (hereditary nonpolyposis colorectal cancer), familial adenomatous polyposis, and Peutz Jeghers syndrome which all predispose to gastric cancer. It also appears that people with blood type A are at increased risk for gastric cancer for an unknown reason.

Hereditary diffuse gastric cancer (HDGC) is an inherited genetic abnormality that is associated with an increased risk of developing gastric cancer. The gene that is abnormal in HDGC is called CDH1 and the abnormality is referred to as a mutation. It is not known how many families carry the CDH1 mutation. Families that have had several cases of gastric cancer, particularly if they are the diffuse type, should consider genetic testing and screening options.

Studies have also linked infection with Helicobacter pylori (H. pylori) with gastric cancer. H. pylori is associated with gastric ulcers and chronic atrophic gastritis, which may explain the higher incidence of gastric cancer in patients infected with H. pylori. However, the exact role of H. pylori in the development of gastric cancer remains unclear. It is theorized that H. pylori causes a gastritis or inflammation of the stomach, which can lead to a loss of secretory cells in the stomach, also known as atrophic gastritis. It is believed that this process of atrophy can lead to gastric cancer. H. pylori has also been linked to lymphomas of the stomach.

Pernicious anemia, an autoimmune disease where the stomach does not produce stomach acid, has also been linked to gastric cancer. 

Keep in mind that just because you have a risk factor for gastric cancer, it does not mean that you are going to get gastric cancer. 

How can I prevent gastric cancer?

Because there is no one risk factor directly associated with gastric cancer, there is no specific way to prevent it. However, there are ways to prevent cancer in general. These include a proper diet low in smoked foods, pickled foods and preserved or heavily salted meats and fish. You should maintain a diet rich in fruits, vegetables and lean proteins. Maintaining a healthy way of life and staying active can also help prevent cancer. 

Don’t start smoking. If you smoke, you should quit as smoking has been shown to cause many types of cancer. If you need help quitting, you should speak with your healthcare provider. 

Since H. pylori infections have been linked to the development of gastric cancers, the quick treatment of H. pylori infections may decrease the numbers of gastric cancers, though whether treating H. Pylori actually reduces the risk of gastric cancer remains controversial. The decision to treat H. pylori should be discussed with your provider.

Studies are continuing to determine if there are other ways to prevent gastric cancer. 

What screening tests are available?

There are no routine screening tests for those at average risk of stomach cancer in the United States. If you have known risk factors such as atrophic gastritis (a chronic inflammation of the stomach lining), you may want to speak to your provider about the need for screening tests. Currently, screening for H. Pylori is not recommended for areas with a relatively low incidence of gastric cancer, such as in the United States.

In Japan, where gastric cancer is much more prevalent, screening programs are used. A variety of tests have been used in these screening programs including: upper gastrointestinal series (barium swallow), upper endoscopies, helicobacter pylori antibody test and serum pepsinogen tests. 

More recently, studies have verified the use of a blood test that could be used to screen for gastric cancer. This analyzes the presence of enzymes in the blood called the serum pepsinogen I/II ratio, which is low in patients at risk for atrophic gastritis and gastric cancer. However, this is still in the early stage of testing. Patients who have an identified HDGC mutation CHD1, should speak to their provider about having a screening EGD.

What are the signs of gastric cancer?

The symptoms of gastric cancer are often nonspecific and early stages don’t often cause symptoms. If you do have symptoms, they can include: 

  • Losing weight which can be related to poor appetite or early satiety (feeling full before finishing a meal). 
  • Discomfort and pain in the belly. 
  • Nausea and vomiting. 
  • Blood in vomit or stool. 
  • Heartburn. 
  • Enlarged belly from fluid buildup. 

These symptoms are often the same symptoms that patients experience when they have peptic ulcer disease or gastritis. Therefore, patients may be treated for benign diseases, such as ulcers, before the cancer diagnosis is made. This is not incorrect management, as gastritis and peptic ulcer disease are much more common than gastric cancer. However, if symptoms persist or do not respond to treatment, further evaluation should be done.

Advanced stages of disease can present with palpable lymph nodes (able to be felt by the healthcare provider) with masses in the area of the belly button, the underarms, or the clavicle. 

How is gastric cancer diagnosed? 

Upper endoscopy is routinely used for the initial diagnosis and staging of patients with gastric cancer. Many times, ultrasound during endoscopy is used to attempt to identify how deep into the wall of the stomach the cancer has penetrated. In addition, ultrasound can identify if the cancer has spread to lymph nodes in many cases. Depth of wall invasion and presence of lymph node spread are two very important components of treatment, as the provider uses this information to determine if surgery is a treatment option.

Other procedures are needed to determine the stage of the disease. CT scans ("CAT scans") of the abdomen and chest may be done, not only to rule out spread to distant organs, like the liver and lungs, but also to determine the spread to lymph nodes close to the stomach that could not be identified by ultrasound. Other tests to rule out abdominal spread of disease outside of the stomach itself arePET scans and laparoscopy.

Laparoscopy is a surgical procedure that involves puncturing the abdominal cavity with a fiber optic camera and directly viewing the organs and tissues in the area of the stomach, the entire abdominal cavity, and the lining of the abdomen (omentum and peritoneum). A sample of abdominal fluid can be sent to cytology/pathology to check for cancer cells in the fluid. 

A biopsy is the removal of a piece of the tissue or fluid for testing to determine if there are cancerous cells. A pathologist, a provider who specializes in looking at biopsy samples, will help determine what type of cancer it is. This can be done to further determine the appropriate treatment plan. 

Other, more routine tests done before treatment include blood screening tests, to insure that overall blood counts are within normal limits, to check for anemia and that a patient's liver and kidneys are functioning properly.

All of these tests are important to determine the extent of the disease, which allows the disease to be staged. The stage provides a guideline for the optimal treatment of the gastric cancer.

How is gastric cancer staged?

Before the staging systems are introduced, here is some background on how cancers grow and spread, and therefore become more advanced in stage.

Cancers cause problems because they spread and can disrupt the functioning of normal organs. One way gastric cancer can spread is by local extension to invade through the stomach wall and into adjacent structures. These surrounding structures include the soft tissues and fat surrounding the stomach as well as other organs such as the spleen, pancreas, large intestine, small intestine, liver, and large blood vessels.

Gastric cancer can also spread by accessing the lymphatic system. The lymphatic circulation is a complete circulation system in the body (somewhat like the blood circulatory system) that drains into various lymph nodes. When cancer cells access this lymphatic circulation, they can travel to lymph nodes and start new sites of cancer. This is called lymphatic spread. Gastric cancers have a propensity to undergo lymphatic spread because there are many small lymphatic vessels contained within the stomach wall. The first lymph nodes that cancer cells spread to are the "perigastric" nodes along the sides of the stomach itself. They can then spread to lymph nodes adjacent to the liver, spleen, pancreas, and aorta.

Gastric cancers can also spread through the bloodstream. Cancer cells gain access to distant organs via the bloodstream and the tumors that arise from these cells are called metastases. Because of the stomach's blood supply, the most common organ it spreads to is the liver, though tumors can also spread to the lung or other organs less commonly.

A fourth way gastric cancer can spread is throughout the entire abdomen, the so-called peritoneal cavity. Although rare, once cancer cells grow outside of the stomach itself, there is nothing stopping cells from spreading to any surface in the entire abdominal cavity.

The staging of a cancer basically describes how much it has grown before the diagnosis is made, documenting the extent of disease. Unfortunately, gastric cancer often presents as a more advanced disease because of lack of early diagnosis, due mainly to the vague associated symptoms. The TNM system is used to describe many types of cancers. Though complicated, this staging system helps providers determine the extent of the cancer, and therefore make treatment decisions regarding a patient's cancer. The stage of cancer, or extent of disease, is based on information gathered through various tests done as the diagnosis and work-up of the cancer is being performed. It has three components: T-describing the extent of the "primary" tumor (the tumor in the stomach itself); N-describing the spread to the lymph nodes; M-describing the spread to other organs (i.e.-metastases). Once the TNM status has been determined, the cancer is given a numeric stage from I-IV, with I representing early disease and IV more advanced disease.  The full AJCC TNM staging system can be found at the end of this article. 

How is gastric cancer treated?

Currently, all curative treatments for gastric cancer involve surgery (surgical resection of the cancer). The smallest amount of surgery that is possible while still taking out all of the cancer is what is normally performed. Generally, tumors that are localized to the part of the stomach closest to the esophagus (proximal stomach) are treated with a gastrectomy (removal of the entire stomach). A partial gastrectomy is the removal of only a portion of the stomach, and a total gastrectomy is removal of the whole stomach. Partial gastrectomies may be appropriate for those tumors located further from the esophagus, in the distal portion of the stomach. Disease involving the entire stomach is also an indication for a total gastrectomy. The surgeon removes the cancer with an adequate margin of healthy tissue and the surrounding lymph nodes. 

It is important that an experienced surgeon performs the dissection, as it is a difficult surgery. Obviously, when the stomach or a portion of the stomach is removed, the two ends must be rejoined. This is done by various procedures, all attempting to eliminate as many of the side effects of the surgery as possible, such as inability to eat larger meals and dumping syndrome. Dumping syndrome results from the stomach being removed and is the result of the small intestine filling too rapidly with undigested food. Symptoms include nausea, vomiting, bloating, diarrhea, and even shortness of breath. These symptoms can usually be managed with dietary modifications.

Although surgery is always required for curative treatment, it is often not enough to achieve cure in many cases. In most patients with more advanced cases of gastric cancer, such as those with positive lymph nodes or tumors which have invaded the deep layers of the stomach or beyond, the cancer will come back if only surgery is done. To combat this, radiation therapy and chemotherapy are recommended for many patients. 

Radiation therapy makes the use of high energy x-rays to kill cancer cells. It does this by damaging the DNA in tumor cells. Normal cells in our body can repair radiation damage much quicker than tumor cells, so while tumor cells are killed by radiation, many normal cells are not. This is the basis for the use of radiation therapy in cancer treatment. Radiation is delivered using large machines that produce the high energy x-rays. After radiation oncologists set up the radiation fields ("radiation fields" are the areas of the body that will be treated by radiation), treatment is begun. Radiation is given 5 days a week for approximately 5 weeks at a radiation treatment center. The treatment takes just a few minutes each day and is painless. The typical radiation field used in the treatment of gastric cancer includes portions of the upper abdomen. In other words, it is designed to kill tumor cells in the area that the surgery was performed. Typical side effects include nausea and vomiting (though this should be less of a problem since the stomach has already been removed) and diarrhea.

Chemotherapy is defined as drugs that are used to kill tumor cells. The large advantage in using chemotherapy is that it travels through the entire body. Hence, if some tumor cells have spread outside of what surgery or radiation can treat, they can potentially be killed by chemotherapy. Similar to radiation, some normal cells are damaged during treatment, resulting in side effects. The standard chemotherapy used in the treatment of gastric cancer is called 5-FU (fluorouracil), coupled with another drug called leucovorin. This type of chemotherapy is delivered through the vein. Sometimes chemotherapy and radiation are used prior to surgery or after surgery (or before AND after surgery) or in combination with radiation. Some of the chemotherapy agents used to treat gastric cancer include: capecitabine, carboplatin, cisplatin, docetaxel, epirubicin, irinotecan, oxaliplatin, paclitaxel and the combination drug trifluiridine and tipiracil

Targeted Therapies

In some cases chemotherapy does not work well in treating gastric cancer. Targeted therapies can be used to treat gastric cancers that have specific targets on their cells. For example, trastuzumab can be used to treat gastric cancer cells that have a HER2 positive protein on them. 

Ramucirumab is used to stop new blood vessels from being created that feed the tumor. VEGF is a protein that tells the body to make new blood vessels. Ramucirumab prevents VEGF from signaling the body to make new blood vessels, which can inhibit the growth of the tumor. 

Immunotherapy

Immunotherapy is the use of medications that help a patient’s own immune system to kill cancer cells. Pembrolizumab is a medication that blocks PD-1, a protein found on T cells. By blocking PD-1 the immune system will start to attack the cancer cells, which can shrink or slow the growth of the tumor.

Clinical Trials                    

Clinical trials are extremely important in furthering our knowledge of this disease. It is through clinical trials that we know what we do today, and many exciting new therapies are currently being tested. Talk to your healthcare provider about participating in clinical trials in your area. You can also explore currently open clinical trials using the OncoLink Clinical Trials Matching Service. 

Follow-up Care and Survivorship

Once a person completes treatment for gastric cancer they need to be closely followed by the oncology team. This close follow-up is required for a couple of reasons. First, to evaluate the patient for side effects related to their treatment. This includes ensuring that the patient has no vomiting or diarrhea and has healed from surgery. Symptoms of "dumping syndrome" may need to be addressed with dietary modifications. In addition, because of the removal of the stomach or a portion of the stomach, gastric cancer patients are prone to a certain type of anemia, resulting from not having enough vitamin B-12. This will be monitored for the patient's entire life, as this anemia does not usually occur until years after the surgery.

It is recommended that a patient is seen every 3 to 6 months following initial treatment for two years then every 6 to 12 months for years 3-5. Labs and imaging studies are done as indicated. Patients do need to be monitored for nutritional deficiencies, especially if they have had surgery.

Fear of recurrence, relationships and sexual health, financial impact of cancer treatment, employment issues, and coping strategies are common emotional and practical issues experienced by gastric cancer survivors. Your healthcare team can identify resources for support and management of these challenges faced during and after cancer.

Cancer survivorship is a relatively new focus of oncology care. With some 15 million cancer survivors in the US alone, there is a need to help patients transition from active treatment to survivorship. What happens next, how do you get back to normal, what should you know and do to live healthy going forward? A survivorship care plan can be a first step in educating yourself about navigating life after cancer and helping you communicate knowledgeably with your healthcare providers. Create a survivorship care plan today on OncoLink.

Resources for Further Reading

Gastric Cancer Foundation

GCF serves as a comprehensive resource for anyone with stomach cancer, their family, friends or caregivers – after a new diagnosis, during treatment and post-treatment. Also operates a Gastric Cancer Registry to assist in research.

No Stomach for Cancer

Empowering families by providing information on stomach cancer and a community of support.

Debbie's Dream Foundation: Curing Stomach Cancer

Raising awareness, funding research, and supporting patients through education, an online community and a clinical trials matching service.

 

Appendix: Staging System for Gastric Cancer

AJCC TNM Staging Classification for Carcinoma of the Stomach, 8th Ed., 2017

Your provider can tell you the TNM staging for your tumor. T stands for the size/invasiveness of the primary tumor. The N describes lymph node involvement and the M describes if the cancer has spread. These numbers are combined to determine the stage of the cancer using the chart below.

Primary Tumor (T)

Description

TX

Primary tumor cannot be assessed

T0

No evidence of primary tumor

T1s

Carcinoma in situ; intraepithelial tumor without invasion of the lamina propria

T1

Tumor invades lamina propria or muscularis mucosae or submucosa

T1a

Tumor invades lamina propria or muscularis mucosae

T1b

Tumor invades submucosa

T2

Tumor invades muscularis propria (without perforation of the visceral peritoneum)

T3

Tumor penetrates subserosal connective tissue without invasion of visceral peritoneum or adjacent structures

T4

Tumor invades serosa (visceral peritoneum) or adjacent structures

T4a

Tumor invades serosa (visceral peritoneum)

T4b

Tumor invades adjacent structures

  

Regional Lymph Nodes (N)

Description

NX

Regional lymph node(s) cannot be assessed

N0

No regional lymph node metastasis

N1

Metastasis in 1-2 regional lymph nodes

N2

Metastasis in 3-6 regional lymph nodes

N3

Metastasis in 7 or more regional lymph nodes

N3a

Metastasis in 7-15 regional lymph nodes

N3b

Metastasis in 16 or more regional lymph nodes

  

Distant Metastasis (M)

Description

M0

No distant metastasis

M1

Distant metastasis

  

Histologic Grade

Description

GX

Grade cannot be assessed

G1

Well differentiated

G2

Moderately differentiated

G3

Poorly differentiated, undifferentiated

  

Clinical Staging

cT

cN

M

Stage 0

Tis

N0

M0

Stage I

T1

T2

N0

N0

M0

M0

Stage IIA

T1

T2

N1, N2, N3

N1, N2, N3

M0

M0

Stage IIB

T3

T4a

N0

N0

M0

M0

Stage III

T3

T4a

N1, N2, N3

N1, N2, N3

M0

M0

Stage IVA

T4b

Any N

M0

Stage IVB

Any T

Any N

M1

  

Pathologic Staging (pTNM)

pT

pN

M

Stage 0

Tis

N0

M0

Stage IA

T1

N0

M0

Stage IB

T1

T1

N1

N0

M0

M0

Stage IIA

T1

T2

T3

N2

N1

N0

M0

M0

M0

Stage IIB

T1

T2

T3

T4a

N3a

N2

N1

N0

M0

M0

M0

M0

Stage IIIA

T2

T3

T4a

T4b

N3a

N2

N1 or N2

N0

M0

M0

M0

M0

Stage IIIB

T1

T2

T3

T4a

T4b

N3b

N3b

N3a

N3a

N1 or N2

M0

M0

M0

M0

M0

Stage IIIC

T3

T4a

T4b

N3b

N3b

N3a or N3b

M0

M0

M0

Stage IV

Any T

Any N

M1

  

Post-Neoadjuvant Therapy (ypTNM)

ypT

ypN

M

Stage I

T1

T2

T1

N0

N0

N1

M0

M0

M0

Stage II

T3

T2

T1

T4a

T3

T2

T1

N0

N1

N2

N0

N1

N2

N3

M0

M0

M0

M0

M0

M0

M0

Stage III

T4a

T3

T2

T4b

T4b

T4a

T3

T4b

T4b

T4a

N1

N2

N3

N0

N1

N2

N3

N2

N3

N3

M0

M0

M0

M0

M0

M0

M0

M0

M0

M0

Stage IV

Any T

Any N

M1

  

References

SEER Statistics, Stomach Cancer, https://seer.cancer.gov/statfacts/html/stomach.html

NCCN Clinical Practice Guidelines, Gastric Cancer, www.nccn.org (log in required)

American Cancer Society, Stomach Cancer, https://www.cancer.org/cancer/stomach-cancer.html

Boku, N. (2014). HER2-positive gastric cancer. Gastric Cancer, 17(1), 1-12.

Cervantes, A., Roda, D., Tarazona, N., Roselló, S., & Pérez-Fidalgo, J. A. (2013). Current questions for the treatment of advanced gastric cancer. Cancer Treatment Reviews, 39(1), 60-67.

Fock, K. M. (2014). Review article: the epidemiology and prevention of gastric cancer. Alimentary Pharmacology & Therapeutics, 40(3), 250-260.

Lordick, F., Allum, W., Carneiro, F., Mitry, E., Tabernero, J., Tan, P., ... & Cervantes, A. (2014). Unmet needs and challenges in gastric cancer: the way forward. Cancer Treatment Reviews, 40(6), 692-700.

McLean, M. H., & El-Omar, E. M. (2014). Genetics of gastric cancer. Nature Reviews Gastroenterology & Hepatology, 11(11), 664-674.

Mickle, M. (2011). Gastric Cancer. In Yarbro C.H, Wujcik, D. & Gobel, B.H. (2011). Cancer Nursing (pp. 1683-1695. Sudbury, MA: Jones and Bartlett.

Orditura, M., Galizia, G., Sforza, V., Gambardella, V., Fabozzi, A., Laterza, M. M., ... & Lieto, E. (2014). Treatment of gastric cancer. World Journal of Gastroenterology, 20(7), 1635-1649.

Oliveira, C., Pinheiro, H., Figueiredo, J., Seruca, R., & Carneiro, F. (2015). Familial gastric cancer: genetic susceptibility, pathology, and implications for management. The Lancet Oncology, 16(2), e60-e70.

Plummer, M., Franceschi, S., Vignat, J., Forman, D., & de Martel, C. (2015). Global burden of gastric cancer attributable to Helicobacter pylori. International Journal of Cancer, 136(2), 487-490.

Rahman, R., Asombang, A. & Ibdah, J. (2014). Characteristics of gastric cancer in Asia. World Journal of Gastroenterology, 20(16), 4483-4490.

Rugge, M., Fassan, M., & Graham, D. Y. (2015). Epidemiology of gastric cancer. In Gastric Cancer (pp. 23-34). Springer International Publishing.

Takahashi, T., Saikawa, Y., & Kitagawa, Y. (2013). Gastric cancer: current status of diagnosis and treatment. Cancers, 5(1), 48-63.

Terashima, M., Iwasaki, Y., Mizusawa, J., Katayama, H., Nakamura, K., Katai, H., ... & Hirao, M. (2015). 2221 Randomized phase III trial of gastrectomy with or without neoadjuvant S-1 plus cisplatin for type 4 or large type 3 gastric cancer; short-term safety and surgical results: Japan Clinical Oncology Group Study (JCOG 0501). European Journal of Cancer, (51), S406.

Tramacere, I., Negri, E., Pelucchi, C., Bagnardi, V...Boffetta, P. (2012). A meta-analysis on alcohol drinking and gastric cancer risk. Annals of Oncology, 23(1), 28-36.

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