Carcinoid Tumour of the Gastrointestinal Tract

Carcinoid tumours of the gastrointestinal tract are slow-growing cancers that often remain silent for years, sometimes discovered only by chance during surgery for other conditions. These rare tumours arise from hormone-producing cells scattered throughout the digestive system and can affect how your body processes food and regulates important chemical signals.

Table of contents

• What is a gastrointestinal carcinoid tumour?
• Where carcinoid tumours develop
• Risk factors
• Signs and symptoms
• Carcinoid syndrome
• Diagnosis and testing
• Prognosis and survival
• Treatment approaches
• Living with carcinoid tumours

What is a gastrointestinal carcinoid tumour?

A gastrointestinal carcinoid tumour is a type of cancer that forms in the lining of the digestive tract. These tumours develop from special cells called neuroendocrine cells, which have characteristics of both nerve cells and hormone-producing cells^[1]. These cells are scattered throughout the chest and abdomen, but most are found in the gastrointestinal tract^[3].

Neuroendocrine cells normally produce hormones that help control digestive juices and the muscles that move food through your stomach and intestines. When these cells become cancerous, they form carcinoid tumours that may also produce and release hormones into your body^[3].

Carcinoid tumours are relatively rare, with an estimated incidence of about one to two cases per 100,000 people in the United States^[19]. However, recent evidence shows that the overall incidence has been steadily increasing over the past 30 years, likely due to improved diagnostic methods^[2][6].

Most gastrointestinal carcinoid tumours are slow-growing. This means you may have a carcinoid tumour for many years and never know it, as many don’t cause symptoms until late in the disease^[2][28].

gastrointestinal neuroendocrine tumor, GI NET, neuroendocrine tumor, carcinoid cancer

Where carcinoid tumours develop

Carcinoid tumours can grow anywhere in the body where there are neuroendocrine cells, but they most commonly occur in the digestive system. This is because the digestive system contains more neuroendocrine cells than any other part of the body^[4].

The most common locations for gastrointestinal carcinoid tumours are^[6][19]:

• Small intestine (30 percent of cases) – particularly the ileum, which is the last part of the small intestine
• Rectum (19.6 percent of cases)
• Appendix – historically the most common site, but now ranks third
• Colon (13 percent of cases)
• Stomach (7 percent of cases)
• Duodenum (first part of the small intestine)

Carcinoid tumours can be classified based on their location in the embryonic gut. Foregut tumours arise in the stomach or upper duodenum. Midgut tumours develop in the small intestine, appendix, or upper colon. Hindgut tumours occur in the lower colon or rectum^[6][19].

Sometimes more than one carcinoid tumour can form in different locations. Carcinoid tumours of the gastrointestinal tract, especially those in the small intestine, are often associated with other cancers. About 29 percent of patients with small intestinal neuroendocrine tumours develop other cancers at the same time or later^[16].

• Stomach
• Small intestine (duodenum, jejunum, ileum)
• Appendix
• Colon
• Rectum
• Gastrointestinal tract
• Liver (when metastases occur)

Risk factors

Several factors may increase your chance of developing a gastrointestinal carcinoid tumour^[3][14]:

• Family history of certain inherited conditions: Having multiple endocrine neoplasia type 1 (MEN1) syndrome or neurofibromatosis type 1 (NF1) syndrome increases risk. These are genetic conditions passed down in families.
• Conditions affecting stomach acid production: Certain conditions that reduce the stomach’s ability to make acid can increase risk, including atrophic gastritis (inflammation causing loss of stomach cells), pernicious anemia (a type of anemia caused by vitamin B12 deficiency), or Zollinger-Ellison syndrome (a condition causing excess stomach acid).
• Age: The average age at diagnosis is 61.4 years^[16].

Having a risk factor does not mean you will definitely develop cancer. Likewise, not having risk factors doesn’t mean you won’t get cancer. If you think you may be at risk, talk to your doctor^[3].

Signs and symptoms

Many gastrointestinal carcinoid tumours don’t cause any signs or symptoms in the early stages. Some tumours, especially those in the stomach or appendix, may never cause symptoms at all. Carcinoid tumours are often discovered accidentally during tests or treatments for other conditions^[3][14].

When symptoms do occur, they are usually vague and depend on where the tumour is located. The most common symptom associated with carcinoid tumours is vague abdominal pain^[6]. Other symptoms may be caused by the tumour’s growth itself or by hormones the tumour produces^[3].

Signs and symptoms in the duodenum (first part of the small intestine) may include^[3][14]:

• Abdominal pain
• Constipation or diarrhea
• Change in stool color
• Nausea and vomiting
• Jaundice (yellowing of the skin and whites of the eyes)
• Heartburn

Signs and symptoms in the jejunum and ileum (middle and last parts of the small intestine) may include^[3][14]:

• Abdominal pain
• Weight loss
• Diarrhea
• Nausea and vomiting
• Bowel obstruction (blockage preventing stool from passing)

Signs and symptoms in the colon may include^[19]:

• Pain
• Loss of appetite
• Weight loss

Signs and symptoms in the rectum may include^[2][19]:

• Rectal bleeding
• Rectal pain
• Constipation

About 40 percent of carcinoid tumours are discovered incidentally during surgery or procedures performed for other reasons^[19]. The diagnosis often occurs either by chance or late in the disease when the tumour causes complications^[6].

Carcinoid syndrome

Carcinoid syndrome is a collection of symptoms caused by hormones released by some carcinoid tumours. This syndrome is rare and occurs when the tumour spreads to the liver or other parts of the body^[3][14].

Carcinoid syndrome is seen in up to 20 percent of patients diagnosed with carcinoid tumours, most commonly when the primary tumour is in the small bowel^[6]. About 95 percent of patients who present with carcinoid syndrome have liver metastases at the time of diagnosis^[6].

The main symptoms of carcinoid syndrome include^[2][6]:

• Skin flushing – redness or a feeling of warmth in the face and neck
• Diarrhea – often watery and occurring frequently
• Wheezing or difficulty breathing
• Pink or purple marks on the skin that look like stretch marks
• Weight gain, particularly around the midsection and upper back
• Heart valve problems, particularly tricuspid regurgitation (leaking of the heart’s tricuspid valve)

Carcinoid syndrome diarrhea occurs in about 80 percent of patients with carcinoid syndrome and poses a substantial burden on quality of life^[18]. Patients with carcinoid syndrome diarrhea frequently report impairment in their daily activities and lifestyle^[18].

The syndrome is caused mainly by serotonin, a hormone that the tumour releases into the bloodstream. When serotonin is broken down by the body, it creates a substance that can be measured in urine tests^[22].

Diagnosis and testing

Diagnosing gastrointestinal carcinoid tumours involves several types of tests to confirm the presence of a tumour and determine its location and extent^[2][11].

Blood tests can detect high levels of hormones secreted by carcinoid tumours or byproducts created when those hormones are broken down by the body^[11]. A common blood test measures chromogranin A, a substance released by neuroendocrine cells^[19].

Urine tests measure excess levels of a chemical called 5-hydroxyindoleacetic acid (5-HIAA), which is produced when the body breaks down serotonin. High levels of this substance in urine can indicate that your body is processing extra serotonin from a carcinoid tumour^[11][19].

Imaging tests help locate the tumour and determine whether it has spread. These may include^[11][19]:

• CT scan (computed tomography) – often used first to examine the abdomen, since most carcinoid tumours are found in the gastrointestinal tract
• MRI (magnetic resonance imaging) – useful in certain situations
• Nuclear medicine scans – including somatostatin receptor imaging using a substance called indium-111 labeled octreotide (OctreoScan), which can help locate tumours
• Ultrasound – particularly endoscopic ultrasound, which uses a scope to get closer images

Endoscopy procedures use a long, thin tube with a lens or camera to examine areas inside your body^[11]:

• Endoscopy – a scope passed down your throat to see inside your upper gastrointestinal tract
• Colonoscopy – a scope passed through your rectum to examine your colon and help diagnose rectal carcinoid tumours
• Capsule endoscopy – swallowing a pill-sized camera to see inside your small intestine

Biopsy involves collecting a sample of tissue from the tumour for laboratory testing to confirm the diagnosis. The type of biopsy depends on where the tumour is located. Sometimes a needle is used to draw cells from the tumour; other times, tissue is collected during surgery^[11].

Prognosis and survival

The outlook for patients with gastrointestinal carcinoid tumours varies widely depending on several factors. Overall, carcinoid tumours tend to follow a more favorable course than most other cancers^[6][9].

Data from a large five-decade analysis of over 13,000 carcinoid tumours revealed that 67.2 percent of patients had a five-year survival rate regardless of the site of the tumour^[2]. However, prognosis depends heavily on the location and stage of the tumour^[2].

Several factors affect prognosis and treatment options^[3][27]:

• Tumour size: Tumours smaller than 1 centimeter rarely show evidence of spread. Those between 1 and 2 centimeters vary in their behavior. Tumours 2 centimeters or larger are almost always invasive or have already spread^[9].
• Location of the primary tumour: Different locations have different prognoses. For example, appendiceal carcinoids have an excellent prognosis with less than 5 percent spreading to other areas when smaller than 2 centimeters^[19].
• Whether the tumour has spread: Tumours that have spread to lymph nodes or the liver have a different outlook than those confined to the original site.
• Whether the tumour can be completely removed by surgery: Complete surgical removal offers the best chance for cure.
• Whether the tumour is newly diagnosed or has come back: Recurrent disease may be more difficult to treat.

All gastrointestinal carcinoids except those in the appendix can enlarge, invade nearby tissues, and spread to other parts of the body if given enough time^[9]. The disease is now considered to be more aggressive and to have a worse prognosis than was previously thought^[2].

Treatment approaches

Treatment for carcinoid tumours depends on the location of the tumour, its size, whether it has spread, and whether it is causing symptoms. Surgical removal is the standard treatment, while medical therapies are often used for symptom relief and to control tumour growth^[6][15].

Surgery is the main treatment for carcinoid tumours and offers the best chance for cure. The type of surgery depends on the tumour’s location^[9][15]:

• For small rectal carcinoids less than 2 centimeters that haven’t invaded deeply, local excision (removing just the tumour) may be sufficient
• For larger tumours or those that have invaded, more extensive surgery may be needed
• When tumours have spread to the liver, surgery may still be performed to remove as much tumour as possible

Most carcinoid tumours are adequately treated by surgery when diagnosed by the pathologist, except for those in the rectum which may require more careful evaluation^[9].

Medications for hormone control are important for managing symptoms, especially in patients with carcinoid syndrome^[15]:

• Somatostatin analogs (such as octreotide) help control symptoms by blocking hormone release. These medications can reduce flushing and diarrhea in most patients with carcinoid syndrome^[15]
• Tryptophan hydroxylase inhibitors (such as telotristat ethyl) work differently by reducing serotonin production and are approved for carcinoid syndrome diarrhea in combination with somatostatin analogs^[15]

Targeted radionuclide therapy uses radioactive substances that attach to tumour cells. Lutetium Lu 177 dotatate (Lutathera) is approved for treating adult patients with certain gastrointestinal neuroendocrine tumours. Studies have shown it can slow tumour growth and cause tumour shrinkage in some patients^[15].

Other systemic therapies may be used for advanced disease^[15]:

• Chemotherapy, typically using drugs like 5-fluorouracil and streptozocin, though response rates rarely exceed 30 percent
• Targeted therapies like everolimus, which has been shown to improve progression-free survival when combined with octreotide
• Interferon-alfa, which may help control symptoms

Liver-directed therapies can be used when tumours have spread to the liver. These include procedures to block blood supply to tumour areas or deliver treatment directly to the liver^[10].

Radiation therapy has mainly a palliative role, particularly for painful bone metastases^[15].

Treatment aims not only to remove or control the tumour but also to manage symptoms and maintain quality of life. Many patients benefit from care provided by a team of specialists who work together to develop a comprehensive treatment plan^[4][12].

Living with carcinoid tumours

Managing life with a carcinoid tumour involves addressing symptoms, making dietary adjustments, and maintaining regular follow-up care.

Managing carcinoid syndrome symptoms is important for maintaining quality of life. Diarrhea is one of the most challenging symptoms. In addition to medications, other causes of diarrhea should be considered in patients with refractory symptoms, including problems absorbing fats, short bowel syndrome, and bile acid malabsorption^[18].

Patients need to be evaluated for dehydration and electrolyte imbalances, which can become life-threatening if sodium and potassium levels get very low. These minerals are critical for normal heart function and blood pressure^[24].

Dietary considerations can help manage symptoms. If you have been diagnosed with a neuroendocrine tumour or carcinoid syndrome, certain foods and eating habits may trigger or worsen symptoms like flushing, diarrhea, gas, bloating, and abdominal pain^[23].

Common triggers to consider avoiding include^[23]:

• Large meals (eat 4 to 6 small meals daily instead)
• High-fat meals
• Alcohol
• Spicy foods
• Raw tomatoes
• Foods containing moderate or high amounts of amines (found in aged cheeses, cured meats, and certain fermented foods)

Everyone is unique, and you may be able to tolerate nearly all or very few of the trigger foods. Keeping a food and symptom diary can help you identify patterns and understand which foods affect you^[23].

Follow-up care is essential. Regular monitoring helps detect any changes in the tumour or development of new problems. This may include periodic blood and urine tests, imaging studies, and visits with your healthcare team^[20].

Because carcinoid tumours of the gastrointestinal tract are associated with other cancers, patients should be evaluated for second primary malignancies^[19].

If you have concerns about symptoms, treatment side effects, or managing daily life with a carcinoid tumour, speak with your healthcare team. They can provide guidance and connect you with resources and support services^[12].