Stomach Cancer Awareness Month
Stomach cancer, also known as gastric cancer, develops when normal cells in the stomach begin to grow out of control. Leran more about the anatomy and function of the stomach, about the many types of stomach cancer, and their treatment options.
How Does Our Stomach Work?
Our stomach is divided into five regions, each of which has various cells or functions. Some cells produce acid and pepsin (a digestive enzyme), which combine to form the gastric juice that aids digestion. Some cells generate a protein called intrinsic factor, which our body requires to absorb vitamin B12. Cancers that develop in different parts of the stomach might cause different symptoms and have different outcomes. The cancer’s location can also influence therapy options.
Our stomach wall consists of five layers, with the mucosa being the innermost. This is where stomach acid and digestive enzymes are produced. The other stomach layers are a supporting layer called the submucosa, a layer of muscles that moves and mixes the stomach content (muscularis propria), and two outer layers (subserosa and outermost serosa) which wrap the stomach.
What Is Stomach Cancer?
Most stomach malignancies begin at the innermost layer and spread through the other layers as they grow. The extend of affected layers play an essential role in defining the stage of cancer and a person’s treatment options and prognosis.
Stomach cancers typically grow gradually over several years. Pre-cancerous alterations in the stomach’s innermost lining frequently occur prior to the development of cancer. These early changes rarely generate symptoms, thus they frequently go undiagnosed. As cancer spreads from the innermost layer to deeper layers, the stage advances, symptoms may become more noticable, and treatment may become more extensive.
Which Types of Stomach Cancer Do We Know?
Adenocarcinomas
Most cancers of the stomach (up to 95%) are adenocarcinomas. These cancers develop from the gland cells in the innermost lining of the stomach.
There are 2 main types of stomach adenocarcinomas:
- Intestinal type: tends to have a slightly better prognosis. The cancer cells are more likely to have certain gene changes that might allow for treatment with targeted drug therapy.
- Diffuse type: tends to grow and spread more quickly. It is less common than the intestinal type, and treatment tends to be more difficult.
The information on the diagnostic and treatment paragraphs of this blog refers to this type of cancer.
Gastrointestinal stromal tumors (GISTs)
These rare tumors start in stem cells in the wall of the stomach called interstitial cells of Cajal. Some GISTs are much more likely than others to grow into other areas or spread to other parts of the body. Although GISTs can start anywhere in the digestive tract, most start in the stomach. For more information, please also read our blog on sarcoma and GISTs.
Neuroendocrine tumors (including carcinoids)
Neuroendocrine tumors (NETs) start in cells in the stomach (or other parts of the digestive tract) that act like nerve cells in some ways and like hormone-making (endocrine) cells in others. Most NETs tend to grow slowly and do not spread to other organs, but some can grow and spread quickly.
Lymphomas
These cancers start in immune system cells called lymphocytes. Lymphomas usually start in other parts of the body, but some can start in the wall of the stomach. The treatment and outlook for these cancers depend on the type of lymphoma and other factors.
Other cancers
Other types of cancer, such as squamous cell carcinomas, small cell carcinomas, and leiomyosarcomas, can also start in the stomach, but these cancers are very rare.
What Are Stomach Cancer Risk Factors
A risk factor is anything that raises your chances of getting a disease, such as cancer. Different cancers have different risk factors. Some risk factors can be avoided, while others, like a person’s age or family history, can’t be changed. Scientists have found several risk factors that make a person more likely to get stomach cancer.
Gender: Stomach cancer is more common in men than in women.
Age: While stomach cancer can develop in younger people, the risk increases over age. The majority of persons diagnosed with stomach cancer are in their 60s, 70s, or 80s.
Helicobacter pylori infection: Helicobacter pylori (H pylori) bacteria are thought to be a major cause of stomach cancer, especially cancers in the lower part of the stomach. Long-term infection of the stomach with this germ may lead to atrophic gastritis and other pre-cancerous changes of the innermost lining of the stomach.
Being overweight or obese: Obesity is linked with an increased risk of cancers of the the upper part of the stomach near the esophagus.
Diet: People whose diets include large amounts of foods preserved by salting (such as salted fish, meat, and pickled vegetables), processed, grilled, or charcoaled meats, and few or no fruits have a higher risk of developing stomach cancers.
Alcohol use: Drinking alcohol increases the risk of stomach cancer, especially in those people who have 3 or more drinks per day.
Tobacco use: Smoking doubles stomach stomach cancer risk, particularly for tumors of the upper part of the stomach near the esophagus.
Previous stomach surgery: Stomach cancer is more likely to occur in people who have had part of their stomach removed to treat non-cancerous disorders like ulcers. This may occur because the stomach produces less acid, allowing more hazardous germs to exist. Reflux of bile from the small intestine into the stomach following surgery may also contribute to higher risk. These tumors usually emerge many years after surgery.
Some types of stomach polyps: Polyps are noncancerous growths on the stomach’s lining. Most polyps such as hyperplastic or inflammatory polyps are unlikely to increase a person’s risk of stomach cancer significantly. However, adenomatous polyps may lead to malignancy.
Inherited cancer syndromes: Some people inherit gene mutations from their parents that lead to conditions that can raise their risk of stomach cancer. These inherited syndromes account for only a small percentage of stomach cancers worldwide. Among them are:
- Lynch syndrome (formerly known as HNPCC): is caused by mutations in one of the mismatch repair (MMR) genes, which normally help repair DNA that has been damaged. Lynch syndrome increases the risk ofcolorectal cancer, stomach cancer, and some other cancers.
- Familial adenomatous polyposis (FAP): FAP is caused by mutations in the APC gene. People with FAP get many polyps in the colon, and sometimes in the stomach and intestines, starting at an early age. People with FAP have a very high risk of getting colorectal cancer and a slightly increased risk of getting stomach cancer.
- Li-Fraumeni syndrome: is caused by a mutation in the TP53 gene. People with Li-Fraumeni syndrome have an increased risk of several types of cancer, including developing stomach cancer at a relatively young age.
- Peutz-Jeghers syndrome (PJS): is caused by mutations in the STK11 gene. People with PJS develop polyps in the stomach and intestines, as well as in other areas including the nose, the airways of the lungs, and the bladder. People with PJS have an increased risk of several types of cancer, including cancers of the colon, pancreas, stomach, and breast.
A family history of stomach cancer: People with first-degree relatives (parents, siblings, or children) who have had stomach cancer are more likely to develop this disease, even without one of the inherited cancer syndromes described above.
Certain occupations: Workers in the coal, metal, and rubber industries seem to have a higher risk of getting stomach cancer.
Signs and Symptoms of Stomach Cancer
Early-stage stomach cancer rarely produces symptoms, or symptoms are unspecific, go unnoticed, or are not taken serious. Therefore, most stomach cancers are discovered after they have grown to a significant size or spread beyond the stomach.
Stomach cancer symptoms and indicators may include:
- poor appetite
- weight loss (without trying)
- abdominal (belly) pain
- discomfort in the abdomen, usually above the navel
- feeling full after eating only a small meal
- heartburn or indigestion
- nausea
- vomiting, with or without blood
- dark brown or black stool due to stomach bleeding
- swelling or fluid in the abdomen
- feeling tired or weak
- yellowing of the skin and eyes (jaundice)
Most of these symptoms are more likely to be caused by things other than stomach cancer, such as a viral infection or an ulcer. However, if you notice any of the symptoms described above, especially if they don’t go away or get worse, see a doctor
How to Diagnose Stomach Cancer
If stomach cancer is suspected, examination will be needed to find out for sure. If cancer is found, additional tests are reqired to define its type and its extend (staging).
Medical History, Physical Examination, and Lab Tests
When taking medical history, the doctor will ask about symptoms such as eating problems, pain, or bloating, and possible risk factors to evaluate if they might suggest stomach cancer or another cause. The physical exam gives information about possible signs of stomach cancer or other health problems. Blood test will check for anemia (a low red blood cell count), which could be caused by the cancer bleeding into the stomach. A stool blood test may detect even minor bleeding from the stomach.
If a stomach cancer or another type of stomach problem is suspected, a referal to a gastroenterologist (a doctor who treats diseases of the digestive tract) is recommended.
Upper Endoscopy
Upper endoscopy (also called esophagogastroduodenoscopy or EGD) is the test most often done when stomach cancer is suspected.
During this test, the doctor passes an endoscope (a thin, flexible, lighted tube with a small video camera on the end) down the patient´s throat. This is done most likely under medication that makes the patient sleepy (sedation).
The inner lining of the esophagus, stomach, and first part of the small intestine can be visually examined. If abnormal areas are seen, biopsy samples can be removed using instruments passed through the endoscope. The tissue samples are sent to a pathology lab to do histology under a microscope – and if necessary a molecular pathology assessment.
Some rare types of stomach cancers, which do start to grow on the inner lining (mucosa) may be hard to detect during an endoscopy.
Imaging Tests
Imaging tests use x-rays, magnetic fields, sound waves, or radioactive substances to create pictures of the inside of the body. To read more details please also visit our Blog on sarcoma diagnosis.
Upper gastrointestinal (GI) series: is an x-ray test to look at the inner lining of the esophagus, stomach, and first part of the small intestine. This test is used less often than upper endoscopy, as it can miss some abnormal areas, and it doesn’t allow the doctor to take biopsy samples. But it is less invasive than endoscopy, and it might be useful in some situations. For this test, the patient drinks a white chalky solution containing a substance called barium. The barium coats the inner lining of the esophagus, stomach, and small intestine and makes it visible in the x-ray pictures.
Computed tomography (CT) scan: uses x-rays to make detailed, cross-sectional images of the soft tissues in the body. CT scans can show the stomach fairly clearly and often can confirm the location of a cancer. CT scans can also show other parts of the body to which stomach cancer might have spread, such as the liver and nearby lymph nodes.
Endoscopic ultrasound (EUS): is often used to see how far a cancer might have spread into the wall of the stomach, or into nearby areas or nearby lymph nodes. For this test, a small ultrasound probe is placed on the tip of an endoscope. Doctors can use these images to look at the layers of the stomach wall, as well as the nearby lymph nodes and other structures just outside the stomach.
Positron emission tomography (PET) scan: can be useful to help determine the extent of the cancer in the body. For this test, a slightly radioactive form of sugar is injected which collects mainly in cancer cells. A special camera is used to create a picture of areas of radioactivity in the body. Although PET scans can be useful for finding areas of cancer spread, they aren’t always helpful in certain kinds of stomach cancer because some types don’t take up much of the radioactive sugar.
Magnetic resonance imaging (MRI): can show detailed images of soft tissues in the body. MRIs use radio waves and strong magnets instead of x-rays. This test is not used as often as CT scans to look for stomach cancer, but it may be helpful in certain situations, such as when looking for tumors in the liver.
Laparoscopy – A Video Inside the Belly
If stomach cancer has already been found, and imaging tests such as CT or PET scans have not shown it has spread to other parts of the body, doctors might do a laparoscopy before any other surgery. This can help confirm the cancer is still only in the stomach, which means surgery to remove it might still be an option.
This procedure is done in an operating room while the patient is sedated. A laparoscope (a thin, flexible tube with a small video camera on the end) is inserted through a small cut in the belly to look closely at the surfaces of the organs and nearby lymph nodes inside the abdomen. It is also possible even remove small samples of tissue, which can then be tested for cancer.
Sometimes, the doctor will “wash” the abdomen with saline (saltwater). This is called peritoneal washing. The fluid is then collected and checked for cancer cells.
Biopsy – To Make Sure
If an abnormal-looking area is seen on endoscopy or an imaging test, the only way to tell for sure if it’s cancer is by doing a biopsy. During a biopsy, the doctor removes small pieces (samples) of the abnormal area.
Biopsies to check for stomach cancer are most often done during an upper endoscopy. If the doctor sees any abnormal areas in the stomach lining during the endoscopy, instruments can be passed down the endoscope to biopsy them.
Some stomach cancers can start deep within the stomach wall, which can make them hard to biopsy with standard endoscopy. If the doctor suspects cancer might be deeper in the stomach wall, endoscopic ultrasound (described below) can be used to guide a thin, hollow needle into the wall of the stomach to get a biopsy sample. CT scans can also be used to guide a biopsy needle into a suspected area.
Biopsies may also be taken from areas of possible cancer spread, such as nearby lymph nodes or suspicious areas in other parts of the body.
How to Test Biopsy Samples – Pathology and Tumor Genetics
Biopsy samples are sent to a pathology lab. Under a microscope the samples are examined fo cancer cells. The way how tumor cells look like, how they grow, and which chemical characteristics they show allows to determine the type of stomach cancer, such as intestinal or diffuse adenocarcinoma, carcinoid tumor, gastrointestinal stromal tumor (GIST), or lymphoma.
More lab tests may be done on the biopsy samples to classify the cancer cells. This may affect how the cancer is treated.
The cancer cells may be tested whether they produce a growth-promoting protein called HER2 using either immunohistochemistry (IHC) or fluorescent in situ hybridization (FISH). Cancers with increased levels of HER2 are called HER2-positive. These cancers can be treated with drugs that target the HER2 protein.
If the cancer cells have a certain amount of the so called immune checkpoint protein PD-L1, or have high levels of microsatellite instability (MSI-H) or a defect in a mismatch repair gene (dMMR), treatment with an immune checkpoint inhibitor might be an option.
If the cells have changes in one of the NTRK genes, certain targeted drugs might be an option for treatment.
The American Cancer Society explans on their Website Testing Biopsy and Cytology Specimens for Cancer how different testing produres used to diagnose cancer, and what the results can tell you. You may also find more information about pathology testing in our Blog on sarcoma diagnosis.
How to Treat Stomach Cancer
Surgery for Stomach Cancer
Surgery can be done for two main reasons:
- Surgery to remove the cancer: Surgery may be done to remove the cancer and part or all of the stomach, as well as some nearby lymph nodes and other structures, depending on the location andof the cancer. The surgeon will try to leave behind as much normal stomach as possible. Sometimes other organs will need to be removed as well.
- Palliative surgery: If the cancer is too widespread to be removed completely, surgery might still be done to help prevent bleeding from the tumor or prevent the stomach from being blocked by tumor growth. This type of surgery can prevent or relieve symptoms, but it is not expected to cure the cancer.
Different types of surgery can be used to try to remove stomach cancer. The type of operation used depends on what part of the stomach is affected by the cancer and how far it has grown into nearby areas. To leave behind as much of the stomach as possible might allow patients to eat more normally afterward. However, the main goal of surgery is to be sure all the cancer has been removed. The surgeon will try to achieve “negative surgical margins”, meaning that no cancer cells are seen at the edges of the removed part of the stomach under a microscope.
Endoscopic resection can be used to treat some very early-stage cancers, when the tumor is located only within the inner layer of the stomach. These procedures do not require a cut in the skin. Instead, the surgeon passes an endoscope down the throat and into the stomach. Surgical tools can be passed through the endoscope to remove the tumor and some layers of the normal stomach wall below and around it.
These operations are done more frequently in some East Asian countries where stomach cancer is more common and more often found at an early stage due to screening. This kind of surgery requires a center that has experience with this technique.
In some centers, operations are done as a laparoscopic gastrectomy, in which long, thin surgical instruments with a small video camera on the end are inserted into the abdomen through several small cuts. Some surgeons do these operations using robotic-assisted laparoscopic surgery. In this technique, the surgeon sits at a control panel and moves robotic arms that have laparoscopic instruments on the ends. Although the laparoscopic approach might result in a shorter hospital stay, less pain after the operation, and a shorter recovery time, this technique is still under development.
No matter which approach is used, it’s important that your surgeon is skilled and experienced with the technique.
Lymph Node Removal
Lymph node dissection or “lymphadenectomy” is a very important part of the operation. Many doctors feel that the success of the surgery is directly related to how many lymph nodes the surgeon removes. It takes a skilled surgeon who is experienced in stomach cancer surgery to remove as many lymph nodes as possible. Studies have shown that the results are better when both the surgeon and the hospital have had extensive experience in treating patients with stomach cancer.
Gastric Bypass
For people with stomach cancer that can’t be removed completely, surgery can often still be used to help control the cancer or to help prevent or relieve symptoms or complications. Because the goal is not to cure the cancer, nearby lymph nodes and parts of other organs usually do not need to be removed.
Tumors in the lower part of the stomach may eventually grow large enough to block food from leaving the stomach. For people healthy enough for surgery, one option to help prevent or treat this is to bypass the lower part of the stomach. This is done by attaching part of the small intestine to the upper part of the stomach, which allows food to leave the stomach through the new connection.
Some people with stomach cancer aren’t able to eat or drink enough to get adequate nutrition. A minor operation can be done to place a feeding tube through the skin of the abdomen and into the lower part of the stomach or into the small intestine. Liquid nutrition can then be put directly into the tube.
Chemotherapy for Stomach Cancer
- Chemotherapy might be used at different times to help treat stomach cancer:
- Chemotherapy which is given before surgery is known as neoadjuvant treatment. It can often shrink the tumor and possibly make surgery easier. It may also help keep the cancer from coming back and help patients live longer.
- Chemotherapy may also be given after surgery has been done to remove the cancer. This is called adjuvant treatment, and its goal is to kill any areas of cancer that may have been left behind but are too small to see. This can help keep the cancer from coming back.
- Chemotherapy may be given as the primary main treatment if the cancer has spread (metastasized) to distant parts of the body, or if it can’t be removed for some other reason. In this case it may help shrink the cancer or slow its growth, which can relieve symptoms and help people live longer.
Immunotherapy for Stomach Cancer
Immunotherapy is the use of medicines to help a person’s own immune system find and destroy cancer cells more effectively.
An important part of the immune system is its ability to prevent itself from attacking normal cells in the body. To do this, it uses “checkpoint” proteins on immune cells, which act like switches turning the immune reaction on off. Cancer cells sometimes use these checkpoints to avoid being attacked by the immune system. Drugs that target these checkpoints (called immune checkpoint inhibitors) can be used to treat some people with stomach cancer.
Nivolumab and pembrolizumab are drugs that target PD-1, a protein on immune system cells called T cells. The PD-1 protein normally helps keep T cells from attacking other cells in the body. By blocking PD-1, these drugs boost the immune response against cancer cells. This can shrink some tumors or slow their growth.
Radiation Therapy for Stomach Cancer
- Radiation can be used in different ways to treat stomach cancer:
- For some earlier stage cancers, radiation can be used along with chemotherapy before surgery to try to shrink the cancer and make it easier to remove.
- After surgery, radiation therapy can be used along with chemotherapy to try to kill any cancer cells that weren’t removed during the surgery. This may help delay or prevent recurrence of the cancer.
- For cancers that can’t be removed by surgery, radiation therapy can sometimes be used to help slow the growth of the cancer and ease symptoms, such as pain, bleeding, or eating problems.
When radiation therapy is used to treat stomach cancer, the radiation is focused on the cancer from a machine outside the body. Special types of radiation therapy use computers to aim the radiation at the cancer from several angles. This can help focus the radiation on the cancer and limit the damage to nearby normal tissues.
Radiation therapy is much like getting an x-ray, but the radiation is much stronger. The treatment itself is painless. However, there may be side effects such as skin problems in areas the radiation passed through, nausea, vomiting, fatigue, or low blood cell counts. There are often ways to relieve them, and they usually go away within a few weeks after the treatment is finished.
Targeted Drug Therapy for Stomach Cancer
Researchers have developed drugs that specifically target the genetic changes in cancer cells. Targeted drugs sometimes work when standard chemothetrapy drugs don’t, and they often have different and less side effects.
Drugs that target HER2: In some people with stomach cancer, the cancer cells have too much of a growth-promoting protein called HER2 on their surface. Cancers with increased levels of HER2 are called HER2-positive. Drugs that target the HER2 protein, such as trastuzumab can often be helpful in treating these cancers.
Drugs that target VEGF: For tumors to grow, they need to make new blood vessels to get blood and nutrients. One of the proteins that tells cells in the body to make new blood vessels is called VEGF (Vascular Epidermal Growth Factor). The VEGF protein does this by attaching to cell surface proteins called VEGF receptors. Ramucirumab is a monoclonal antibody that binds to a VEGF receptor and inhibits the effect of VEGF. This can help slow or stop the growth of some cancers.
TRK inhibitors: A very small number of stomach cancers have changes in one of the NTRK genes. This causes them to make abnormal TRK proteins, which can lead to abnormal cell growth and cancer. Larotrectinib and entrectinib are medicines that can be used to treat advanced cancers with NTRK gene changes that are still growing despite other treatments.
Drug that target CLDN18.2: CLauDiN 18.2 is a protein that plays an important role in keeping healthy epithelial cells bound together. Epithelial cells are cells that are commonly found along the gastrointestinal tract. When an epithelial cell turns into a cancer cell, CLDN18.2 may atypically move to the surface of the cancer cell. Zolbetuximab is a monoclonal antibody that targets CLDN18.2 and may be used to treat advanced stomach cancer that express high amounts of CLDN18.2 on their cell surface.
Treatment Choices May be Difficult in Stomach Cancer
Treatment of stomach cancer depends largely on where the cancer is in the stomach and how far it has spread. Because most people will get different types of treatment for their cancer, it’s important that a team of doctors review and discuss the best options for treatment. Stomach cancer can be challenging to treat, so it’s important that the cancer care team is experienced in treating it.
Yet, also factors such as a person’s age, overall health, and preferences, can be important as well. Therefore, as a patient it is important to know all the options, with advantages, disadvatages and risks. An oncology treatment should be done in a shared decision making. To be able to contribute in this important decision, patients and their loved need information and empowerment. TheKnowHow is commited to support this process.
We found a list of questions on the American Cancer Society Website which may support you and your loved ones to prepare for doctors visits in case you are confronted with a stomach cancer diagnosis .
TheKnowHow Independent Second Opinion Service
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