Gastric Neuroendocrine Tumours

Gastric neuroendocrine tumours (NETs), also known as gastric carcinoid tumours, are rare cancers that develop in the stomach, an organ in the upper abdomenstomach, stomach area, belly that stores and digests food. They are known as a type of gastrointestinal carcinoid tumoura tissue mass that forms from groups of unhealthy cells, also known as gastroenteropancreatic NETs (GEP-NETs).

The stomach has four tissue layers: the mucosa, submucosa, muscle layer and outer layer. The mucosa is the inner-most layer that produces digestive juices (specifically hydrochloric acid and pepsin) to break down food, and mucus to protect the lining of the stomach. The second inner-most layer, the submucosa, supports the mucosa layer, and provides blood and nutrients to the stomach. It contains a variety of bloodthe red bodily fluid that transports oxygen and other nutrients around the body vessels, lymphatic vessels, and nerves. The next layer is the muscle layer, also known as the muscularis externa, which is responsible for producing contractions to further help break down food and push it to the small intestinea section of the gastrointestinal tract that recieves food from the stomach and absorbs the nutrients from food, also called small bowel. The outer-most layer is the serosa, which is a smooth, protective membrane that surrounds the stomach.

Neuroendocrine cancers are a complex group of tumours that develop in the neuroendocrine system, which is responsible for regulating important bodily functions such as heart rate, blood pressure and metabolism. They most commonly develop in the gastro-intestinal tract, pancreasa long, flat organ that sits between the stomach and the spine that plays a key role in digestion and blood sugar regulation, and the lungs; however, they can develop anywhere in the body. These tumours develop from neuroendocrine cellsthe basic structural and functional unit of all living things, which are responsible for receiving signals from the nervous system and producing hormones and peptides (small proteins) in response.

Gastric NETS are generally diagnosed in people over the age of 50, with gender predilection varying by subtype. However, anyone can develop this disease.

Types of Gastric Neuroendocrine Tumours

There are three primary types of gastric NETs, which are classified by associated conditions and the hormones they produce. Some experts argue that there is a fourth subtype, however more research into this area is required.

Type I

Type I gastric NETs are the most common subtype of this disease, and often begin as benignnot cancerous, can grow but will not spread to other body parts growths – or polyps – in the lining of the stomach, which can become cancerous if left untreated. Type I gastric NETs are often associated with atrophic gastritis (chronica long-lasting disease that changes slowly over time inflammation of the stomach), autoimmune gastritis and/or infectiona condition where harmful pathogens, such as bacteria, viruses or parasites, have entered the body with helicobacter pylori bacteria, as well as an overproduction of the hormonea chemical substance produced by glands in the endocrine system that regulates various functions in the body gastrin. This type of gastric NET is slightly more common in women and is likely to recur, but often has a good prognosisto predict how a disease/condition may progress and what the outcome might be.

Type II

Type II gastric NETs are a less common subtype of this disease, and often occur as a result of multiple endocrine neoplasia type 1 (MEN 1) and/or Zollinger-Ellison syndrome. It may cause the overproduction of the hormone gastrin by a tumour called gastrinoma, which can cause an over-production of stomach acid. These tumours are often quite small, and can have a good prognosis.

Type III

Type III gastric NETs are the second most common type of gastric NETs. These tumours are usually larger that types I and II, and are not related to the overproduction of gastrin. These tumours are slightly more common in males and are likely to metastasise, but can have a good prognosis when caught early.

Treatment

If a gastric NET is detected, it will be staged and graded based on size, metastasiswhen the cancer has spread to other parts of the body, also known as mets, and how the cancera disease where abnormal cells split without control and spread to other nearby body tissue and/or organs cells look under the microscope. Stagingthe process of determining how big the cancer is, where it started and if it has spread to other areas and grading helps your doctors determine the best treatment for you.

Cancers can be staged using the TNM staging system:

• T (tumour) indicates the size and depth of the tumour.

• N (nodea small lump or mass of tissue in your body) indicates whether the cancer has spread to nearby lymph nodessmall bean-shaped structures that filters harmful substances from lymph fluid.

• M (metastasis) indicates whether the cancer has spread to other parts of the body.

This system can also be used in combination with a numerical value, from stage 0-IV:

• Stage 0: this stage describes cancer cells in the place of origin (or ‘in situ’) that have not spread to nearby tissuea group of cells that work together to perform a function.

• Stage I: cancer cells have begun to spread to nearby tissue. It is not deeply embedded into nearby tissue and had not spread to lymph nodes. This stage is also known as early-stage cancer.

• Stage II: cancer cells have grown deeper into nearby tissue. Lymph nodes may or may not be affected. This is also known as localisedaffecting only one area of body cancer.

• Stage III: the cancer has become larger and has grown deeper into nearby tissue. Lymph nodes are generally affected at this stage. This is also known as localised cancer.
• Stage IV: the cancer has spread to other tissues and organs in the body. This is also known as advancedat a late stage, far along or metastatic cancer.

Cancers can also be graded based on the rate of growth and how likely they are to spread:

• Gradea description of how abnormal cancer cells and tissue look under a microscope when compared to healthy cells I: cancer cells present as slightly abnormal and are usually slow growing. This is also known as a low-grade tumour.

• Grade II: cancer cells present as abnormal and grow faster than grade-I tumours. This is also known as an intermediate-grade tumour.
• Grade III: cancer cells present as very abnormal and grow quickly. This is also known as a high-grade tumour.

Once your tumour has been staged and graded, your doctor may recommend genetic testinga procedure that analyses DNA to identify changes in genes, chromosomes and proteins, which can be used to analyse tumour DNA to help determine which treatment has the greatest chance of success, which analyses your tumour DNA and can help determine which treatment has the greatest chance of success. This is often performed after a biopsyremoval of a section of tissue to analyse for cancer cells, and can help guide treatment options for you.

Treatment is dependent on several factors, including location, stage of disease and overall health.

Treatment options for gastric NETs may include:

• Surgerytreatment involving removal of cancerous tissue and/or tumours and a margin of healthy tissue around it to reduce recurrence, potentially including:

• • Endoscopic mucosal resectiona minimally invasive procedure that uses an endoscope to remove cancer or abnormal growths/tissue from the lining of the gastrointestinal tract.

• • Gastrectomycomplete or partial removal of the stomach.

• • Surgery to insert a feeding tube (often required after surgery on the stomach), such as a gastronomy tube (G-tube)a feeding tube surgically inserted through an incision in the abdominal wall directly into the stomach to get fluids/food/liquids to and from the stomach or nasogastric tube (NG tube)a thin, soft tube that goes in through the nose, down the throat, and into the stomach to get fluids/food/liquids to and from the stomach, also known as a NG tube.

• Somatostatin analogues (SSAs)medication used to inhibit excessive hormone production  .

• Chemotherapya cancer treatment that uses drugs to kill or slow the growth of cancer cells, while minimising damage to healthy cells.

• Radiation therapya treatment that uses controlled doses of radiation to damage or kill cancer cells, potentially including peptide receptor radionuclide therapy (PRRT)a targeted cancer treatment that uses radioactive substances (radionuclides) to deliver radiation directly to tumour cells.

• Targeted therapymedication that targets specific molecular features of cancer cells.

• Ablation therapya minimally invasive procedure that uses extremely high or low temperatures to destroy (ablate) abnormal tissue and/or cancer cells.

• Watch and waitthe close monitoring of a cancer without giving treatment until symptoms appear or worsen (for slow growing tumours).

• Clinical trialsresearch studies performed to test new treatments, tests or procedures and evaluate their effectiveness on various diseases.
• Palliative carea variety of practices and exercises used to provide pain relief and improve quality of life without curing the disease.

Risk factors

While the cause of gastric NETs remains unknown, the following factors may increase the likelihood of disease:

• Chronic inflammation of the stomach, often associated with atrophic or autoimmune gastritis.
• Having multiple endocrine neoplasia syndrome type 1 (MEN1).

Symptoms

Some people with gastric NETs will appear asymptomatic in the early stages of disease. As the tumour progresses, some of the following symptoms may appear:

• Abdominal discomfort and/or pain.

• Nauseato feel sick or likely to vomit and/or vomiting.

• Reflux, heartburn and/or indigestion.

• Feeling full after eating little food.

• Unexplained weight loss/loss of appetite.

• Anaemiaa condition where there aren't enough red blood cells in the blood, causing fatigue, weakness and pale skin and affecting how the body responds to infection.

• Zollinger-Elison syndrome, which carries its own set of symptoms:

• Abdominal pain.

• Nausea and/or vomiting.

• Weight loss.

• Diarrhoeafrequent discharge of watery or loose stools from the body.

• Darkening of stoolwaste product from the bowel sent to the anus for removal; also known as faeces or poo colour/rectal bleeding.

• Carcinoid syndrome (rare), which carries its own set of symptoms:

• • Facial flushing (usually red or purple in the face, neck, and/or upper chest).

• • Diarrhoea.

• • Wheezing.

• • Abdominal pain.

• • Carcinoid heart disease (plaques on the heart muscle caused by excess hormone production).

• • Fatiguea state of extreme tiredness or exhaustion, can be physical or mental.

• • Skin changes, such as red or purple spots on the face, neck, and/or upper chest.

• Paraneoplastic syndromesa group of rare disorders that occur when the immune system has a reaction to a cancerous tumour within the body (rare).

• Hypercalcaemiaexcess levels of calcium in the blood (rare).

Not everyone with the symptoms above will have cancer, but see your general practitioner (GP) if you are concerned.

Diagnosis

If your doctor suspects you have a gastric NET, they may order the following tests to confirm the diagnosisthe process of identifying a disease based on signs and symptoms, patient history and medical test results and refer you to a specialist for treatment:

• Physical examinationan examination of your current symptoms, affected area(s) and overall medical history.

• Imagingtests that create detailed images of areas inside the body tests, potentially including:

• • Ultrasounda type of medical imaging that uses soundwaves to create detailed images of the body  /endoscopic ultrasound.

• • MRI (magnetic resonance imaging)a type of medical imaging that uses radiowaves, a strong magnet and computer technology to create detailed images of the body.

• • CT (computed tomography) scana type of medical imaging that uses x-rays and computer technology to create detailed images of the body.

• • PET (positron emission tomography) scana type of medical imaging that uses radioactive tracers to create detailed images of the body.

• • MIBG scana type of medical imaging that uses radioactive tracers to detect overactive parathyroid glands or neuroendocrine tumours; also known as a MIBI or sestamibi scan.

• Blood teststesting done to measure the levels of certain substances in the blood.

• Urine teststesting done to measure the levels of certain substances in the urine.

• Exploratory surgeryan exploratory surgical procedure used for conditions that cannot be confirmed by scans and tests alone, such as a gastroscopyexamination of the stomach and part of the small bowel with a small, flexible instrument known as a gastroscope.

• Biopsy.

References

• Cancer Research UK
• Neuroendocrine Cancer Australia
• Neuroendocrine Cancer UK