Gastrointestinal carcinoid tumours (GCTs), also known as gastroenteropancreatic NETs (GEP-NETs), are neuroendocrine tumours that develop in the gastrointestinal tract. Most commonly, they develop in the small intestines, rectum, and appendix, however, they can also develop in the stomach, large intestines, and pancreas.

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. 

GCTs are generally more common in women, and are often diagnosed in people around 60 years old. However, anyone can develop this disease.

Types of Gastrointestinal Carcinoid Tumours

There are several different types of GCTs, which are often categorised by their location.

Gastric NETs

Gastric neuroendocrine tumours (gastric NETs) are rare NETs that develop in the stomach, an organ in the upper abdomen that stores and digests food. There are four main types of gastric NETs.

Type I

Type I gastric NETs are the most common subtype of this disease, and often begin as benign 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 (chronic inflammation of the stomach), and an overproduction of the hormone gastrin. This type of gastric NET is likely to recur, but often has a good prognosis.

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). 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 likely to metastasise, but can have a good prognosis when caught early.

Type IV

Type IV gastric NETs are the rarest subtype of gastric NETs. These tumours tend to be the largest, and are at a late stage when diagnosed. These tumours may not have as good of a prognosis as other gastric NETs.

Small Bowel NETs

Small bowel NETs are rare NETs that develop in the small bowel, which is a long, hollow tube that carries the food from the stomach to the large bowel. It is made up of three separate sections: the duodenum, jejunum, and ileum. NETs can develop in any of these sections. 

Duodenal NETs

Duodenal NETs are found in the duodenum, the first portion of the small bowel. They are rarer than other types of small bowel NETs, and can produce high levels of hormones such as serotonin, calcitonin, gastrin, and somatostatin, depending on the type of tumour you have. While they can be aggressive, they can have a good prognosis.

Ileum and Jejunum NETs

NETs of the ileum and jejunum are more common than duodenal NETs, and are often difficult to
diagnose. They may be slow-growing, asymptomatic, and small, and are often diagnosed at a later
stage of disease. While these NETs can metastasise, they can have a good prognosis.

Appendiceal NETs

Appendiceal NETs are a rare type of NET that develops in the appendix, a small, thin, tubular pouch that is attached to the large bowel. These tumours often produce symptoms similar to those produced by an appendicitis, and are often diagnosed during surgery to remove the appendix (appendectomy).  Appendiceal NETs can have a good prognosis.

Goblet Cell Carcinoma (GCCs)

Goblet cell carcinomas (GCC) are rare neuroendocrine tumours that develop in the appendix. More specifically, they develop in goblet cells, which are responsible for mucus secretion and production. 

GCCs demonstrate a unique combination of both neuroendocrine cells and adenocarcinoma cells, which are cancerous cells that develop from mucus-producing cells. They tend to be more aggressive than classic neuroendocrine tumours, but are classified and staged as carcinomas of the appendix.

For more information on GCCs, please refer to the Rare Cancers Australia Goblet Cell Carcinoma (GCC) page.

Large Bowel NETs

Large bowel NETs are rare NETs that develop in the large bowel, the long, hollow, tube that is the last part of the gastrointestinal tract. It is composed of three main sections – the caecum, colon, and rectum. NETs can develop in any of these sections.

Colon NETs

Colon NETs are a very rare type of NET that develops in the colon, the largest, middle portion of the large bowel. These tumours are often large and aggressive, and are often likely to metastasise. Colon NETs can have a good prognosis when caught early.

Rectal NETs

Rectal NETs are a common type of GCT that develops in the rectum, the end portion of the large bowel that connects to the anus. In many cases, rectal NETs are asymptomatic, and are often found by accident. As they are asymptomatic, they are often diagnosed at a late stage of disease, and may have metastasised. Rectal NETs can have a good prognosis.

Pancreatic NETs

Pancreatic NETs (pNETs), or islet cell tumours, are rare carcinomas (cancers arising from bone and soft tissue lining organs) that develop in the pancreas. The pancreas is a long, flat organ that sits between the stomach and the spine. Pancreatic NETs are often divided into functioning (produce hormones) and non-functioning (don’t produce hormones) categories.

Types of pNETs include:

• Gastrinoma.
• Glucagonoma.
• Insulinoma.
• Non-functional pNETs.
• Somatostatinoma.
• VIPoma.

Treatment 

If a GCT 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 GCTs may include:

• Surgery, potentially including:
  • Endoscopic resection (removal of the tumour via an endoscopy). 
  • Subtotal/partial gastrectomy (partial removal of the stomach).
  • Total gastrectomy (complete removal of the stomach). 
  • Surgery to insert a feeding tube (often required after surgery on the stomach). 
  • Right or left hemicolectomy (removal of the left or right side of the colon).
  • Sigmoid colectomy (removal of the sigmoid colon).
  • Total colectomy (complete removal of the colon). 
  • Proctocolectomy (removal of the colon and rectum).
  • High anterior resection (removal of the lower end of the colon and the upper end of the rectum).
  • Abdominoperineal resection or excision (APR or APE) (removal of the sigmoid colon, rectum, and anus).
  • Ultra-low anterior resection (removal of the lower end of the colon and all of the rectum).
  • Colonic J-pouch (an internal pouch is created from the lining of the bowel, which acts as the rectum).
  • Appendectomy (complete removal of the appendix).
  • Pancreaticoduodenectomy (Whipple procedure) (removal of portions of the pancreas, bile duct, duodenum and/or gallbladder).
  • Distal pancreatectomy (removal of the tail of the pancreas and the spleen).
  • Total pancreatectomy (complete removal of the pancreas and the spleen). 
• Radiation therapy, potentially including:
  • Peptide receptor radionuclide therapy (PRRT).
  • Selective internal radiation therapy (SIRT).
• Chemotherapy.
• Somatostatin analogues (SSAs).
• Targeted therapy, potentially including:
  • Monoclonal antibodies.
  • Small molecular inhibitors.
• Hormone therapy.
• Cryotherapy.
• Radiofrequency ablation (RFA).
• Watch and wait.
• Clinical trials.
• Palliative care.

For more information on the treatment options, please refer to the Rare Cancers Australia Treatment Options page.

Risk factors 

While the cause of GCTs remain unknown, the following factors may increase the likelihood of developing the disease:

• Family history of cancer.
• Having conditions such as:
  • Pre-existing stomach conditions, such as peptic ulcers.
  • Type 2 diabetes.
  • Multiple endocrine neoplasia type 1 (MEN1).
  • Neurofibromatosis type 1 (NF1).
  • Von Hippel-Lindau (VHL) disease.
  • Tuberous sclerosis.
• Long-term use of proton pump inhibitors.
• 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 

Some patients with a GCT will appear asymptomatic in the early stages of disease. As symptoms progress, some of the following symptoms may appear. 

• Carcinoid syndrome, 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).
  • Fatigue.
  • Skin changes, such as red or purple spots on the face, neck, and/or upper chest.
• Rectal bleeding.
• Bowel obstruction.
• Mass in the abdomen. 
• Zollinger-Elison syndrome (most common in gastric NETs):
  • Abdominal pain.
  • Nausea and/or vomiting.
  • Weight loss.
  • Diarrhoea.
• Anaemia.

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

Diagnosis/diagnosing 

If your doctor suspects you have a GCT, 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.  
• Serum VIP test, which measures levels of VIP in the blood.
• Stool analysis, which measures sodium (salt) and potassium levels in your stool.

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 

You may require an exploratory procedure if the imaging scans were inconclusive. Some of these procedures include an endoscopy (inserting a long, flexible tube with a light and small camera through the oesophagus and into the stomach), a colonoscopy (inserting a long, flexible tube with a light attached (colonoscope) through your anus to examine the rectum and colon), and/or a flexible sigmoidoscopy (the instrument passed through the anus is shorter (sigmoidoscope) and only examines the rectum and lower portion of the colon).

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 GCTs 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 

• Australian Cancer Research Foundation
• GICancer.org
• Neuroendocrine Cancer Australia

^{Some references are to overseas websites. There may be references to drugs and clinical trials that are not available here in Australia.}