An overview of neuroendocrine tumours
Neuroendocrine tumours are rare. They start in neuroendocrine cells - these are specialised nerve cells that produce hormones. Neuroendocrine cells are part of the endocrine system, which is a network of glands in the body. The glands produce hormones.
Hormones control many of the body’s functions by controlling the levels of particular chemicals and fluids in the body, and they help us respond to changes in our environment.
Neuroendocrine tumours occur most commonly in the digestive system but can occur in other parts of the body. They can be non-cancerous (benign) or cancerous (malignant).
Some neuroendocrine tumours produce hormones which can cause particular symptoms, such as diarrhoea, flushing of the skin and wheezing. Tumours that produce hormones are called functioning (hormone-secreting). Tumours that don't produce hormones are known as non-functioning (non-hormone secreting).
Types of neuroendocrine tumour:
- Carcinoid
- GEPs - Gastroenteropancreatic tumours - which include:
- insulinomas
- gastrinomas
- glucagonomas
- VIPomas
- somatostatinomas
1. Carcinoid tumours
Carcinoid tumours
A carcinoid tumour, sometimes referred to as simply 'carcinoid', is a tumour of the neuroendocrine system. The neuroendocrine system is a network of glands that produce particular hormones and send them into the bloodstream to affect the function of different organs in the body.
Most carcinoid tumours are found in the appendix or the small bowel (intestine). Less commonly, they may arise in the lung or the pancreas. Rarely, they may arise in other parts of the body.
Carcinoid tumours often grow slowly and it may be several years before any symptoms appear and the tumour is diagnosed.
Causes of a carcinoid tumour
This is a rare type of tumour. Approximately 1200 new carcinoid tumours are diagnosed each year in the UK. Men and women are affected equally and carcinoid is usually found in adults over the age of 30. As with many other forms of cancer, the exact cause is unknown.
Signs and symptoms
The type of symptoms will depend on where the tumour started, where it may have spread to, and whether it produces a hormone known as serotonin. If a carcinoid tumour starts in the appendix it does not usually spread to other parts of the body and does not produce serotonin. As a result there are very few symptoms and it is often discovered by chance when the appendix is removed for another reason.
Carcinoid syndrome
If a carcinoid tumour starts outside the appendix, and particularly if it spreads to the liver, it will often produce serotonin and cause symptoms known as carcinoid syndrome. Symptoms include:
- diarrhoea
- flushing of the skin
- wheezing (similar to asthma)
- loss of appetite
- weight loss
It may be possible to reduce the symptoms of carcinoid syndrome by avoiding substances or conditions that cause flushing, such as alcohol and stress.
How it is diagnosed
Before your doctor can make a firm diagnosis of a carcinoid tumour a number of tests will have to be done.
Urine test When serotonin is broken down in the liver, it is excreted as a chemical called 5HIAA in the urine. Your urine will be collected over a 24-hour period to check whether there are raised levels of 5HIAA.
Blood tests may be taken to check serotonin levels.
The doctor may also carry out a number of tests to find out whether the cancer has spread.
X-rays and scans These may be taken to show if there has been any spread of the tumour.
Chest x-ray This will show whether there has been any spread to the lungs.
Ultrasound scan A simple, painless scan which uses sound waves to form a picture of the inside of the abdomen.
CT (computerised tomography) scan A CT scan takes a series of x-rays to build up a three-dimensional picture of the inside of the body. The scan is painless but takes longer than an x-ray (about 30 minutes). It may be used to find where the cancer started (the primary tumour) or to check for any spread of the disease (secondaries or metastases).
MRI (magnetic resonance imaging) scan This scan uses magnetism instead of x-rays to form a series of cross-sectional pictures of the inside of the body. During the scan you will be asked to lie very still on a couch inside a metal cylinder. The test can take up to an hour and is completely painless, although the machine is quite noisy. If you don’t like enclosed spaces you may find the machine claustrophobic.
Octreotide scan An octreotide scan examines how several of your internal organs are working. Octreotide is a substance that is absorbed by carcinoid cells. It can show where a cancer started and any areas that it has spread to. The scan is done in the nuclear medicine department and takes place over three consecutive days.
On the first day you will go to the department twice. In the morning you will have an injection in your arm. You are then usually free to stay in or leave the hospital. In the afternoon you will have a scan taken using a gamma camera. The scan takes about an hour and during this time you will lie still on a bed. On the following two afternoons pictures will again be taken for up to one and a half hours.
123MIBG scan A drug called 123MIBG may be used to show up the site of a carcinoid tumour. 123MIBG is a mildly radioactive drug that is absorbed by carcinoid cells. The scan takes place over two consecutive days in the nuclear medicine department.
On the first day you will go to the department twice. In the morning you will be given an injection in the arm. You are then usually free to stay or leave the hospital. You will go back to the department in the afternoon to have a scan with a gamma camera lasting for about an hour. The following morning you will have further pictures taken for about one and a quarter hours. At this point you may be given a further injection of 123MIBG.
Biopsy A small sample of cells is taken from the tumour to be examined under a microscope. Depending on which part of the body is affected, a local or general anaesthetic is given.
Treatment
The treatment for a carcinoid tumour depends on a number of factors including your general health and the size and position of the tumour. The results of your tests will enable your doctor to discuss the best type of treatment with you.
Surgery
If the tumour is contained in one area (localised), or if there has been only limited spread (regional), surgery is usually the first choice of treatment. If it is possible to remove the tumour completely no other treatment may be necessary.
If the tumour has spread to other parts of the body (metastatic) but there are only one or two areas – for example, in the liver – surgery may still be possible because of the slow growth of the tumour.
Chemotherapy
Chemotherapy is the use of anti-cancer (cytotoxic) drugs to destroy cancer cells. It may sometimes be used to treat carcinoid tumours that have spread, with the intention of reducing the tumour and the secretion of serotonin, and of prolonging a good quality of life.
Interferon
Another type of drug treatment for the symptoms of carcinoid tumours is interferon, which is a biological therapy. Interferon is given as an injection under the skin. At first it can cause flu-like symptoms such as chills, fever, aching joints and tiredness, but these usually disappear.
Radiotherapy
For this treatment, high-energy rays are used to destroy cancer cells. Radiotherapy is usually given to treat symptoms, such as pain, which may occur if the tumour has spread to the bones.
Hepatic artery embolisation
This treatment may be used to slow down the growth of secondary liver tumours (metastases) by reducing the blood supply to the liver. Sometimes it is combined with chemotherapy. The procedure usually requires an anaesthetic, and you will probably have to stay in hospital overnight. You may feel unwell and your temperature may be raised for a few days afterwards.
131MIBG
Another drug, 131MIBG, may be used to reduce the number of carcinoid cells and the symptoms of carcinoid syndrome. It gives a dose of radiotherapy to the carcinoid cells, and is known as targeted radiotherapy. This treatment can be given as a drink or as an injection into the vein.
Radio-labelled octreotide
Octreotide is absorbed by carcinoid cells. A small dose of radioactivity can be attached to it. This treatment is given as an injection into a vein in the arm. Again, it can reduce the number of carcinoid cells.
Radiofrequency ablation
This may be used in some situations where the tumour is affecting the liver. It uses laser or radiowaves (microwaves) to destroy the cancer cells by heating them to high temperatures. A sedative drug is given to make the person feel drowsy and a local anaesthetic is used to numb the skin of the abdomen. A fine needle is then inserted through the skin over the liver and into the centre of the tumour. Powerful laser light or radiowaves are then passed through the needle and into the tumour, which heats the cancer cells and destroys them.
Treatments for carcinoid syndrome
Somatostatin analogues
Carcinoid syndrome can be treated with drugs known as somatostatin analogues. These work by reducing the production of hormones by the tumour, and can help to reduce the flushing and diarrhoea.
The somatostatin analogue octreotide (Sandostatin®) is given as a short-acting injection under the skin up to three times a day. Most people are taught how to give the injection themselves.
Other somatostatin analogues are given as longer-acting injections into the muscle (intramuscular) between 7 and 28 days apart, depending on the drug that is used and the response. Commonly used drugs are octreotide (Sandostatin Lar®) and lanreotide (Somatuline® LA, Somatuline Autogel®).
Clinical trials
Research into treatments for carcinoid tumours is ongoing and advances are being made. Cancer doctors use clinical trials to assess new treatments.
You may be asked to take part in a clinical trial. Your doctor must discuss the treatment with you, so that you have a full understanding of the trial and what it means to take part.
Your feelings
During your diagnosis and treatment you are likely to experience a number of different emotions, from shock and disbelief to fear and anger. At times these emotions can be overwhelming and hard to control. It is quite natural, and important, to be able to express them. Everyone has their own ways of coping with difficult situations; some people find it helpful to talk to friends or family, while others prefer to seek help from people outside their situation. Others prefer to keep their feelings to themselves. There is no right or wrong way to cope, but help is available if you need it.
2. Gastroenteropancreatic tumours (GEPs)
Neuroendocrine tumours (NETs)
NETs are a rare group of tumours that start in the cells of the neuroendocrine (pronounced new-row-en-doe-crin) system.
The neuroendocrine system is a network of endocrine glands and cells throughout the body. Endocrine glands produce and release hormones that are circulated around the body. The hormones control the levels of particular chemicals and fluids in the body and help us respond to changes in our environment.
Neuroendocrine tumours can be non-cancerous (benign) or cancerous (malignant). This information focuses on the malignant types of neuroendocrine tumours affecting the gastrointestinal tract (the GI tract). The GI tract is the digestive system.
When a tumour develops in part of the neuroendocrine system, it often causes too much of a certain hormone to be produced.
The type of hormone overproduced depends on the type of gland that is affected by the tumour.
Some tumours may not cause an over-production of any hormones and may not cause any obvious symptoms. These are known as non-functioning NETs.
Many of these tumours, even if they appear cancerous under the microscope or have spread, may be very slow-growing and may even appear to stop growing for a long time.
NETs are classified depending on:
- the type of cell in which the tumour starts
- the part of the body affected
- the particular endocrine glands that are involved.
Gastroenteropancreatic tumours
Most gastroenteropancreatic tumours (GEPs) develop in the organs of the digestive system. They usually start in the cells of the stomach (gastro), intestines (entero) and the pancreas.
The different types of GEP are named after cells where they develop. Some of these include:
- insulinomas
- gastrinomas
- glucagonomas
- VIPomas
- somatostatinomas.
Sometimes the primary site (where the cancer started) cannot be found. In this situation, the cancer may be found when it has spread to a different part of the body, such as the liver, and has formed a secondary tumour (metastasis).
Causes
The exact cause of GEPs is unknown. However, the risk of developing one is increased in people with Multiple Endocrine Neoplasia 1 and 2 (MEN 1 and MEN 2). These conditions are usually caused by inherited faulty genes. The affected person may develop tumours in several different endocrine organs. MEN 1 and MEN 2 can affect both males and females. Genetic testing can be carried out for people with a family history of MEN.
Signs and symptoms
The signs and symptoms will depend on where the tumour is in the body, and whether it is producing extra hormones.
Insulinomas
Insulinomas can occur in any part of the pancreas. The pancreas produces insulin, which controls the level of sugar in the blood. When there is an abnormally high level of insulin in the body, this causes a fall in the blood-sugar level (hypoglycaemia).
A low blood-sugar level causes symptoms which can include:
- headaches
- confusion
- trembling and palpitations
- anxiety
- eyesight changes
- possible fits (seizures)
- weakness.
A low blood-sugar level is most likely to occur first thing in the morning, when exercising or after missing a meal. It can often be relieved by eating food or by having sugary drinks.
Gastrinomas
Gastrinomas (gas-trin-oma) often start in the pancreas or the upper part of the small bowel (duodenum). They usually produce too much of the hormone gastrin. Gastrin causes the production of gastric acid. If too much gastric acid is produced, it can lead to ulcers in the stomach, gullet (oesophagus) and the small bowel (small intestine). There may be several ulcers and they tend not to respond well to the usual ulcer medicines in normal doses. This is often called Zollinger-Ellison syndrome.
Common symptoms can include:
- bleeding into the stomach
- perforation of the wall of the stomach or duodenum
- narrowing of part of the bowel (stricture)
- diarrhoea
- steatorhoea (pale, greasy and offensive smelling stools)
- inflammation of the lining of the gullet (oesophagitis).
Glucagonomas
Glucagonomas (glue-ca-gone-oma) occur most often in the pancreas. Glucagonomas usually produce too much of the hormone glucagon. Glucagon is another hormone that controls the level of sugar in the body.
Common symptoms can include:
- anaemia (low level of haemoglobin in the blood)
- weight loss
- diabetes (sugar intolerance)
- a skin rash
- blood clots.
VIPomas
VIPomas usually occur in the pancreas. They can produce too much of a substance called vasoactive intestinal peptide.
Common symptoms can include:
- excessive watery diarrhoea
- low levels of potassium as a result of the diarrhoea
- weakness and tiredness
- nausea and vomiting.
Somatostatinomas
Somatostatinomas (pronounced so-mat-o-stat-tin-oma) are extremely rare tumours that usually occur in the pancreas, duodenum or jejunum (parts of the small intestine).
Common symptoms can include:
- steatorhoea (pale, greasy and offensive smelling stools)
- weight loss
- anaemia (low level of haemoglobin in the blood)
- pain in the affected area
- diarrhoea
- diabetes.
It is important to remember that many of the symptoms of tumours of the neuroendocrine system are the same as the symptoms of other, non-cancerous, conditions.
How GEPs are diagnosed
GEPs can be very difficult to diagnose. Before a diagnosis can be made, your doctor will ask you about your past medical conditions, including any symptoms that you have.
A number of tests will be done. These may include any of the following:
Blood and urine tests Several samples of blood and urine are taken to look for the levels of particular hormones. A sample of urine may be collected over a 24-hour period. Sometimes it is necessary to fast overnight before having certain blood tests. These tests may be repeated to monitor any ongoing changes in hormone levels.
X-rays and scans A combination of x-rays and scans will be taken to find where the tumour is and if it has spread.
Ultrasound of the abdomen This test uses sound waves to make up a picture of the abdomen and surrounding organs. It is done in the hospital scanning department. You will be asked not to eat, and to drink clear fluids only (nothing fizzy or milky) for 4–6 hours before the scan. Once you are lying comfortably on your back, a gel is spread onto your abdomen. A small device like a microphone is then rubbed over the area. The sound waves are converted into a picture using a computer. The test is completely painless and takes about 15–20 minutes.
Endoscopic ultrasound A flexible tube (endoscope) is inserted into the mouth, down the throat, and into the digestive system. An ultrasound is attached to the end of the endoscope. This enables the doctor to examine the digestive system organs more closely.
123MIBG scan A drug called 123MIBG may be used to show up the site of a GEP. 123MIBG is a mildly radioactive drug that is absorbed by GEP cells. The scan takes place over two consecutive days in the nuclear medicine department. On the first day you will go to the department twice. In the morning you will be given an injection in the arm. You are then free to stay or to leave the hospital. You will go back to the department in the afternoon to have a scan with a gamma camera lasting for about an hour. The following morning you will have further pictures taken for about one and a quarter hours. At this point you may be given a further injection.
Octreotide scan This scan examines how several of your internal organs are working. Octreotide (ock-tree-o-tide) is a substance that is absorbed by GEP cells. It can show where a cancer started and where it has spread. The scan is done in the nuclear medicine department and takes place over three consecutive days. On the first day you will go to the department twice. In the morning you will have an injection in your arm. You are then free to stay in or leave the hospital. In the afternoon you will have a scan taken using a gamma camera. The scan takes about an hour and during this time you will lie still on a bed. On the following two afternoons pictures will be taken for up to one and a half hours.
CT (computerised tomography) scan This is a series of x-rays that builds up a three-dimensional picture of the inside of the body. The scan is painless and takes about 30 minutes. It may be used to find where a tumour started and can also show whether a tumour has spread.
MRI (magnetic resonance imaging) scan This type of scan uses magnetism (not x-rays) to form a series of cross-sectional pictures of the inside of the body. During the scan you will be asked to lie very still on the couch inside a metal cylinder. The test can take up to an hour and is completely painless, although the machine is quite noisy. If you don’t like enclosed spaces you may find the machine claustrophobic.
PET (positron emission tomography) scan A PET scan uses low-dose radioactive sugar to measure the activity of cells in different parts of the body. Areas of cancer are usually more active than normal tissue and show up on the scan. If you need a PET scan you might have to travel to a specialist centre to have one. PET scans are not always routinely carried out as specialists have different opinions as to whether they are more helpful than other investigations.
Biopsy A small sample of cells (a biopsy) is taken from the tumour to be examined under a microscope. The biopsy may be taken using ultrasound or CT scans to make sure that the sample is taken from the tumour. Depending on which part of the body is affected, a local or general anaesthetic is given.
Surgical treatment
Treatment will depend on a number of factors and varies from person to person.
Surgery
If the tumour is contained in one area (localised), or if there has been only limited spread, surgery is usually the first choice of treatment. If it is possible to remove the tumour completely, no other treatment may be necessary.
If the tumour has spread to other parts of the body (metastatic), surgery may still be possible to remove the part of the tumour that is producing too many hormones. This is often referred to as tumour debulking.
If a GEP is blocking an organ, such as the bowel, surgery may be helpful to relieve the blockage (obstruction).
Liver surgery
If the tumour has spread to the liver, surgery can be used to remove the parts of the liver containing the tumour. Very occasionally, a liver transplant may be considered for people with a particularly slow-growing tumour affecting the liver.
Non surgical treatments
Somatostatin analogues
Somatostatin analogues are drugs that have been found to be effective in controlling certain symptoms that GEPs can cause. They work by blocking the release of specific hormones. Commonly used somatostatin analogues are octreotide and lanreotide. Octreotide (Sandostatin®) is given as a short-acting injection under the skin (subcutaneously) up to three times a day. You, or a family member, can be taught to give the injection. Longer-acting injections of octreotide (Sandostatin Lar®) or lanreotide (Somatuline® LA, Somatuline Autogel®) can also be given. These injections are given deep under the skin, from once a week to once every four weeks, depending upon the drug used and the situation.
Chemotherapy
This is the use of anti-cancer (cytotoxic) drugs to destroy cancer cells. It may sometimes be used to treat GEPs that have spread, to reduce the size of the tumour and lower the levels of hormones they produce. Chemotherapy is often used for GEPs of the pancreas. However, as these may be very slow-growing tumours, your doctor may not think it is appropriate to use chemotherapy if your situation appears to be stable.
Embolisation
Sometimes blocking the blood supply to the tumours can slow down the growth of GEPs. This is called embolisation and is done by putting a temporary tube into the artery that provides the blood supply to the tumour. Then a substance is injected to block the artery. This can be particularly useful for people with slow-growing tumours affecting the liver.
Interferon
Another type of drug treatment for the symptoms of GEPs is interferon, which is a biological therapy. Interferon is given as an injection under the skin. At first it can cause flu-like symptoms such as chills, fever, aching joints and tiredness, but these usually disappear.
Targeted radiotherapy
131MIBG
A drug called 131MIBG may be used to reduce the number of tumour cells and the symptoms of GEP tumours. It gives a dose of radiotherapy to the tumour cells, and is known as targeted radiotherapy. This treatment can be given as a drink or as an injection into the vein.
Radio-labelled octreotide
Octreotide is absorbed by neuroendocrine cells. A small dose of radioactivity can be attached to it. This treatment is given as an injection into a vein in the arm. It can reduce the number of neuroendocrine cells.
If you have targeted radiotherapy, you may need to be in a room by yourself for a few days so that other people around you are not unnecessarily exposed to the radiotherapy.
Radiofrequency ablation
This may be used in some situations where the tumour is affecting the liver. It uses laser or radiowaves (microwaves) to destroy the cancer cells by heating them to high temperatures. A sedative drug is given to make the person feel drowsy and a local anaesthetic used to numb the skin of the abdomen. A fine needle is then inserted through the skin over the liver and into the centre of the tumour. Powerful laser light or radiowaves are then passed through the needle and into the tumour, which heats the cancer cells and destroys them.
Treating symptoms
Sometimes medicines such as antacids will be given to reduce the amounts of acid in the stomach. Other drugs may be used to control your blood sugar or to control diarrhoea.
Clinical trials
Research into treatments for GEP tumours is ongoing and advances are being made. Cancer doctors use clinical trials to assess new treatments.
You may be asked to take part in a clinical trial. Your doctor must discuss the treatment with you so that you have a full understanding of the trial and what it means to take part.
Your feelings
You may have many different emotions including anger, resentment, guilt, anxiety and fear. These are all normal reactions and are part of the process many people go through in trying to come to terms with their illness.
