Gastroesophageal Junction Adenocarcinoma

Gastroesophageal junction adenocarcinomas are staged and treated the same as cancers of the esophagus and are typically considered to be a form of esophageal cancer.

The esophagus is the tube that allows food to travel from the mouth to the stomach. The lower part of the esophagus that connects to the stomach is called the gastroesophageal (GE) junction. At this location, there is a ring of muscles called the lower esophageal sphincter. This muscular ring controls the movement of food from the esophagus into the stomach. The GE junction lies just below the diaphragm, or breathing muscle, beneath the lungs.

Cancers that start in glandular cells are termed adenocarcinomas. Therefore, a gastroesophageal junction adenocarcinoma is a cancer that begins in glandular cells located near the GE junction. This cancer has also been referred to as esophagogastric junction adenocarcinoma.

Gastroesophageal junction adenocarcinomas are staged and treated the same as cancers of the esophagus and are typically considered to be a form of esophageal cancer.

Esophageal cancer is four times more common in men than in women. Almost 17,000 cases of new esophageal cancer cases are diagnosed yearly in the U.S., and the condition causes over 15,500 deaths each year. It is most common in Caucasians, but the incidence rate in African-Americans is almost as high as in whites. Esophageal cancer is much more common in other parts of the world, including Iran, northern China, India, and southern Africa.

Risk factors that can increase the risk of gastroesophageal adenocarcinoma include the following:

• Male gender
• Increasing age (over 85% of cases occur in people over 55)
• Gastroesophageal reflux disease (GERD) and Barrett's esophagus, a change in the lining of the esophagus that occurs after long-term reflux of stomach acid into the lower esophagus
• Tobacco use, including chewing tobacco, cigars, and pipes
• Alcohol use, although alcohol increase the risk of other types of esophageal cancer more than for gastroesophageal adenocarcinoma
• Obesity
• Dietary factors: A diet high in fruits and vegetables decrease the risk, while consumption of processed meat may increase the risk.
• Achalasia, a disorder of movement of the esophagus

The cause of GE junction adenocarcinoma is not well understood. As with all cancers, the DNA from esophageal cancer cells shows changes in many different genes. But specific genetic changes (mutations) that have been definitively linked to GE junction adenocarcinoma are not well characterized. Inherited DNA mutations can increase some people's risk for developing certain cancers, but this does not seem to be the case for esophageal cancer as it does not appear to run in families. There are known risk factors (see below) that can increase your risk of getting esophageal cancer.

Most esophageal cancers, including gastroesophageal junction adenocarcinomas, do not cause symptoms until they have grown large or spread to an advanced stage. At this point, they cause typical symptoms and signs. The symptoms and signs may include the following:

• Dysphagia, or difficulty swallowing, can be a sense that food is "stuck" in the esophagus or not going down properly. Others have described a feeling of choking on food. If the opening of the esophagus is very narrow due to a cancer, people might start avoiding bread and meat due to difficulty eating and switching to a more liquid diet that can pass easily into the stomach.
• Increased production of saliva: The body compensates for difficulty swallowing by producing more saliva. This can lead to coughing up mucus or excessive saliva.
• Hoarseness
• Unintentional weight loss
• Painful swallowing or heartburn-like chest pain (chronic GERD) or burning
• Nausea and vomiting
• Chronic cough or hiccups
• Black stool from bleeding in the area of the cancer (GI bleeding)
• Anemia
• Bone pain, if the cancer has spread to the bones

You doctor may order a number of different tests to diagnose gastroesophageal junction adenocarcinoma.

• Upper endoscopy is a procedure in which doctors use a flexible lighted tube to examine the inside of the esophagus and the GE junction. With this instrument, samples (biopsies) of any suspicious or abnormal areas can be taken for analysis by a pathologist to determine if cancer is present. Sometimes the biopsy tissue will show precancerous changes, known as dysplasia.
• Endoscopic ultrasound is often performed with an endoscopy. This uses an ultrasound probe that gives off sound waves at the end of the endoscope. This allows to doctor to determine the size of an esophageal cancer and the extent to which it has spread into nearby areas, including spread to nearby lymph nodes.
• Barium swallow is a procedure in which a contrast material (barium) is swallowed prior to taking a series of X-ray images of the esophagus, stomach, and part of the intestines. This is called an upper gastrointestinal (GI) series.
• CT scans, PET scans, and MRI scans are other imaging studies that may be used to help diagnose gastroesophageal junction adenocarcinoma or determine the extent of spread of the tumor.

After diagnosis, the tumor is staged. That means the extent to which the tumor has spread is assessed and classified. Staging helps determine the proper type of treatment. Staging is done using a "T, N, M" system. The "T" refers to the location of the tumor and how deep into the wall of the esophagus it has grown. Some tumors will grow entirely through the wall of the esophagus and into adjacent structures like the trachea, aorta, or spine. The "N" refers to the degree to which the tumor has spread to lymph nodes, and "M" refers to the presence of distant metastases, meaning that tumor cells have entered the bloodstream and caused the cancer to spread to distant locations in the body.

The tumor grade is also assessed based on how the cells appear when examined under the microscope. A low-grade (grade 1) tumor contains cells that are closest to resembling normal cells, while high-grade (grade 3) tumors have cells that appear markedly different from normal cells. Grade 2 tumors fall somewhere in between.

Once these characteristics have been determined, the cancer is assigned to a stage group from I to IV. Some of these numerical groups are further subdivided into A-C.

Treatment for gastroesophageal junction adenocarcinoma is dependent upon the tumor stage and can involve a combination of different methods.

Surgery

Surgical removal (resection) of the tumor is indicated when possible. Stage I and II esophageal cancers are potentially removable, along with most stage III cancers, if they have not grown into important organs like the windpipe or aorta. Stage IV tumors have spread to distant sites in the body and are not able to be removed by surgery. Cancers of the gastroesophageal junction, when possible, are treated by surgically removing part of the stomach, the cancer, and a portion of the normal esophagus above the cancer. The stomach is then connected to the remaining part of the esophagus. Nearby lymph nodes are also removed to check for the presence of cancer cells.

Neoadjuvant therapy is treatment that is given before surgery to try to shrink the tumor to make the surgery easier. Neoadjuvant therapy may be given in the form of radiation or chemotherapy or a combination of the two.

Endoscopic therapy

Endoscopic mucosal resection (EMR) is a technique that removes sections of the lining of the esophagus, done through an endoscope as described above. This technique is only suitable for very small early stage cancers.

Photodynamic therapy (PDT) is also used to treat small cancers and precancerous changes. Porfimer sodium (Photofrin), a light-activating drug, is first injected into a vein. The drug collects in cancer cells over a time period of a few days. Using an endoscope, a laser light is then directed on the cancer. The drug reacts with the light and changes into a substance that destroys cancer cells, which are later removed with an endoscope. This can be used to remove small cancers or to reduce the size of large cancers to improve swallowing ability. It is limited in its ability to only destroy parts of the tumor that can be accessed by the laser light source, so deeper parts of the tumor cannot be treated.

Other treatments including electrocoagulation and laser ablation are sometimes carried out to keep the esophagus open and help the affected person swallow. These involve the localized destruction of cancer cells using laser or electric energy. Placement of a stent to keep the esophagus open is also sometimes performed via endoscopy.

Chemotherapy

Chemotherapy involves the administration of drugs into the body that kill rapidly dividing cancer cells. Chemotherapy may be given after surgery (in this case known as adjuvant therapy) or prior to surgery to shrink a tumor (neoadjuvant therapy). It is often given along with radiation therapy.

Different chemotherapy drugs have been used to treat gastroesophageal junction cancers. A regimen known as ECF, consisting of epirubicin (Ellence), cisplatin, and 5-fluoruracil (5-FU), is often given for gastroesophageal junction tumors. Other drugs that have been used include carboplatin, paclitaxel (Taxol), docetaxel (Taxotere), capecitabine (Xeloda), oxaliplatin, and irinotecan (Captosar).

Radiation therapy

Radiation therapy uses high-energy particles or rays to destroy cancer cells. It may be given along with chemotherapy (known as chemoradiation), either before or after surgery. It can also be used to relieve symptoms in the cases of advanced gastroesophageal junction cancer like pain, bleeding, and trouble swallowing. This type of treatment is referred to as palliative treatment or palliation.

Targeted therapy

Targeted therapy drugs are medicines that work against a particular molecular abnormality or "target" found on cancer cells. This is a newer type of treatment than chemotherapy.

Trastuzumab (Herceptin) and ramucirumab (Cyramza) are two targeted therapy drugs that have been used to treat advanced esophageal cancers. Trastuzumab is used to treat cancers that over express a protein known as HER-2 that drives cell growth. Ramucirumab targets a protein known as VEGF that directs cancers to make new blood vessels. Ramucirumab is used to treat advanced cancers of the gastroesophageal (GE) junction, typically when other drugs have stopped working.

Immunotherapy

A new type of cancer treatment involves the use of drugs that target so-called "checkpoints" of the immune system. The normal immune system has built-in checkpoints that protect the body from attacks by its own immune system. Pembrolizumab (Keytruda) is a drug that blocks a known immune system checkpoint.. It targets PD-1, a protein on immune system T cells that helps keep these cells from attacking normal cells in the body. By blocking PD-1, the drug stimulates the body to mount an immune response against cancer cells. This drug has been used in some people with advanced gastroesophageal junction adenocarcinomas who have had at least two previous treatments that have stopped working.

Survival rates for cancers are usually expressed as five-year survival rates. These statistics are based upon people who were diagnosed at least five years ago, so survival rates may be improved for those diagnosed more recently due to advances in treatment. In general, survival rates increase as the stage (extent of spread of the cancer at diagnosis) increases. It is important to note that these survival rates are only estimates, and individuals may have different outcomes based upon a number of factors.

Five-year survival rates for esophageal cancers have been reported for tumors that are either localized, with regional spread to nearby lymph nodes, or with distant spread. These are combined rates for all types of esophageal cancer, which includes gastroesophageal junction adenocarcinomas. Adenocarcinomas (cancers of glandular cells) tend to have a slightly more favorable survival rate than other types of esophageal cancer.

• Localized: Cancers of the esophagus that are confined to the esophagus have a five-year survival rate of 43%.
• Regional: Cancers of the esophagus that have spread to lymph nodes in the area have a five-year survival rate of 23%.
• Distant: This group includes all stage IV cancers that have spread to distant sites in the body. These cancers have a five-year survival rate of 5%.

It is impossible to completely prevent gastroesophageal adenocarcinoma, but you can take steps to decrease your risk. Getting adequate treatment if you have been diagnosed with GERD or Barrett's esophagus can lower your risk. Eating a healthy diet and maintaining a healthy weight can decrease the risk. Reducing alcohol use and not using tobacco can also lower your risk.