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Tuesday, May 20, 2008

Gastroenteropancreatic tumours (GEPs)

This information is about a rare group of neuroendocrine tumours (NETs) called gastroenteropancreatic tumours (GEPs). We hope that the information will answer any questions that you may have about them. If you have any further questions you can ask your doctor or nurse at the hospital where you are having your treatment.

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.

The digestive system
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).


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 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 (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 (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 usually occur in the pancreas. They can produce too much of a substance called vasoactive intestinal peptide.

Common symptoms can include:


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.


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.


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.


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.


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


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.


This section has been compiled using information from a number of reliable sources, including:

  • Oxford Textbook of Oncology (2nd edition). Souhami et al. Oxford University Press, 2002.
  • Gastrointestinal Oncology: Principles and Practice. Kelsen et al. Lippincott Williams and Wilkins, Philadelphia, 2002.
  • The Textbook of Uncommon Cancers (2nd edition). Raghavan et al. Wiley, 1999.
  • Endocrine Tumours. Clark et al. Ontario, BC Decker Inc, 2003.

For further references, please see the general bibliography.

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