Pancreatic neuroendocrine tumours (pNETs), or islet cell tumours, are rare carcinomas (cancers arising from bone and soft tissue lining the organs) that develop in the pancreas. The pancreas is a long, flat organ that sits between the stomach and the spine. It has two primary functions; endocrine function, which is responsible for secreting hormones (such as insulin) to control blood sugar levels, and exocrine function, which produce pancreatic enzymes that aid in digestion.
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, pancreas, and the lungs; however, they can develop anywhere in the body. These tumours develop from neuroendocrine cells, which are responsible for receiving signals from the nervous system and producing hormones and peptides (small proteins) in response.
This page will focus on a specific type of functional pNET called gastrinoma, which is a tumour that develops from G-cells in the pancreas. These cells are responsible for the production and secretion of the gastrin hormone. Gastrin is responsible for the production of stomach acids that aid in digestion. Advanced gastrinomas may lead to Zollinger-Ellison syndrome.
pNETs have a higher incidence in males and are generally diagnosed in people over 55; however, people of any age and sex can develop this disease.
Treatment
If a gastrinoma is detected, it will be staged and graded based on size, metastasis (whether the cancer has spread to other parts of the body) and how the cancer cells look under the microscope. Staging 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 (nodes) indicates whether the cancer has spread to nearby lymph nodes.
- 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 tissue.
- 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 localised 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 advanced or metastatic cancer.
Cancers can also be graded based on the rate of growth and how likely they are to spread:
- Grade 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 testing, which analyses your tumour DNA and can help determine which treatment has the greatest chance of success. They will then discuss the most appropriate treatment option for you.
Treatment is dependent on several factors, including location, stage of disease and overall health.
Treatment options for gastrinomas may include:
- Surgery, potentially including:
- Local excision of the tumour.
- Pancreatoduodenectomy/Whipple procedure (removal of of affected portions of the pancreas, gallbladder, stomach, small intestine and/or lymph nodes).
- Total pancreatectomy (complete removal of the pancreas).
- Somatostatin analogues (SSAs).
- Radiation therapy, potentially including peptide receptor radionuclide therapy (PRRT).
- Chemotherapy.
- Clinical trials.
- Palliative care.
For more information on the treatment options, please refer to the Rare Cancers Australia Treatment Options page.
Risk factors
The risk factors for this disease are similar across all types of pNETs. They include:
- Family history of cancer.
- Having conditions such as:
- Being a smoker or having a history of smoking.
- Excessive alcohol intake.
- Obesity.
Not everyone with these risk factors will develop the disease, and some people who have the disease may have none of these risk factors. See your general practitioner (GP) if you are concerned.
Early symptoms
Unlike non-functional pNETs, functional tumours such as gastrinoma may present symptoms in the early stages of the disease. The symptoms of gastrinoma are caused by excessive gastrin production, which may lead to the following symptoms:
- Chronic peptic/stomach ulcers.
- Abdominal and/or back pain.
- Gastro-oesophageal reflux (where stomach contents regress into the oesophagus).
- Diarrhea.
- Oesophagitis.
- Nausea and/or vomiting.
Not everyone with the symptoms above will have cancer, but see your GP if you are concerned.
Diagnosis/diagnosing
If your doctor suspects you have a gastrinoma, they will order a range of diagnostic tests to confirm the diagnosis, and refer you to a specialist for treatment.
Physical examination
Your doctor will collect your overall medical history, as well as your current symptoms. Following this, they may examine your body to check for any abnormalities.
Endocrine studies & blood tests
Endocrine studies involve blood and/or urine tests and imaging tests (see below) to analyse your hormone levels and detect any abnormalities. Some of these tests may include:
- General blood test to assess overall health.
- Blood chemistry and/or blood hormone studies, which analyse the levels of certain hormones and other substances in the blood.
- Chromogranin A test, which analyse the levels of Chromogranin A and other hormones (such as insulin, gastrin, and glucagon) in the blood. This test can be used as a differential procedure to determine whether the tumour is functional or non-functional.
- Fasting serum gastrin test, which analyses gastrin levels after a period of fasting.
- Basal acid output test, which analyses the amount of stomach acid is produced after a period of fasting.
- Secretin stimulation test, where a secretin drug is injected to produce stomach acid, which is then analysed to observe any abnormalities.
Imaging tests
The doctor will take images of your body using magnetic resonance imaging (MRI), a computed tomography scan (CT scan), x-rays, ultrasounds, bone scans and/or positron emission tomography (PET scan), depending on where it is suspected the cancer is. The doctor may also look at other parts of the body and look for signs of metastasis. Your doctor may also recommend a somatostatin receptor scintigraphy scan, which involves injecting a radioactive substance into the bloodstream which attaches to the tumour and shows where the tumour(s) are located in the body.
Exploratory surgeries & biopsy
In some cases, an exploratory surgery is required in order to properly confirm the diagnosis. This is often done in the form of a laparotomy, which creates an abdominal incision to check for signs of disease.
Once the location(s) of the cancer has been identified, the doctor will perform a biopsy to remove a section of tissue using a needle. The tissue sample will then be analysed for cancer cells. This can be done by a fine needle aspiration (FNA), a core needle biopsy (CNB), or during an exploratory surgery.
Prognosis (Certain factors affect the prognosis and treatment options)
While it is not possible to predict the exact course of the disease, your doctor may be able to give you a general idea based on the rate and depth of tumour growth, susceptibility to treatment, age, overall fitness, and medical history. Generally, early-stage gastrinomas have a better prognosis and survival rates. However, if the cancer is advanced and has spread, the prognosis may not be as good and there may be a higher risk of cancer recurrence. It is very important to discuss your individual circumstances with your doctor to better understand your prognosis.
References
Some references are to overseas websites. There may be references to drugs and clinical trials that are not available here in Australia.