Gastroenteropancreatic Neuroendocrine Tumour Disease

Gastroenteropancreatic neuroendocrine tumours are rare growths that develop from hormone-producing cells in the digestive system and pancreas, often growing slowly over many years and sometimes not causing symptoms until they have spread to other parts of the body.

Table of contents

• What are gastroenteropancreatic neuroendocrine tumours?
• Other names for this condition
• Parts of the body affected
• Types of tumours
• How common is this condition?
• Causes and risk factors
• Signs and symptoms
• How doctors diagnose GEP-NETs
• Treatment approaches
• Outlook and survival
• Living with GEP-NETs

What are gastroenteropancreatic neuroendocrine tumours?

Gastroenteropancreatic neuroendocrine tumours (GEP-NETs) are growths that develop from neuroendocrine cells – special cells that work like both nerve cells and hormone-making cells. These tumours can form anywhere in the digestive system or pancreas^[3].

GEP-NETs are considered rare, though doctors are finding them more often now than in the past. The most recent data shows the number of cases has increased by more than 400% over 29 years, rising from 1.09 per 100,000 people in 1973 to 5.25 per 100,000 in 2004^[3]. This increase is likely due to better testing methods that can detect these tumours earlier^[12].

Most GEP-NETs grow slowly and can take many years to form^[5]. People are usually diagnosed in their 50s, which is younger than for many other digestive system cancers^[3].

carcinoid tumors, islet cell tumors, GEP-NETs

Other names for this condition

Healthcare providers may use different names for gastroenteropancreatic neuroendocrine tumours. They are sometimes called carcinoid tumours or islet cell tumours, especially when they form in the pancreas^[3][5].

Parts of the body affected

GEP-NETs can develop in several organs within the digestive system. Doctors traditionally group them based on which part of the digestive tract they affect^[3][9]:

• Esophagus (food pipe)
• Stomach
• Small intestine (duodenum, jejunum, ileum)
• Large intestine (colon)
• Rectum
• Appendix
• Pancreas
• Liver

Most GEP-NETs occur in the small intestine, rectum, and appendix^[10]. The pancreas is the third most common location^[2].

Types of tumours

GEP-NETs can be grouped in different ways. One important distinction is whether they release extra hormones into the body^[2][5].

Functional and nonfunctional tumours

Functional tumours make and release extra hormones that cause specific symptoms. Some pancreatic tumours release insulin, which controls blood sugar. Others release gastrin, which helps with digestion^[2].

Nonfunctional tumours do not make extra hormones. These are more common than functional tumours. They may still cause symptoms if they grow large enough to affect nearby organs^[5].

Specific types of functional tumours

Several types of functional pancreatic tumours are named after the hormone they produce^[2][4][5]:

• Insulinomas are the most common type of functioning pancreatic tumour. They release insulin, which keeps blood sugar from getting too high. About 10% of insulinomas are cancerous
• Gastrinomas release gastrin, which triggers the stomach to make acid. About 60% of gastrinomas are cancerous
• Glucagonomas release glucagon, which keeps blood sugar from getting too low. These are often cancerous
• VIPomas release a substance called vasoactive intestinal peptide, which relaxes muscles in the stomach and bowels
• Somatostatinomas release somatostatin, which manages several body functions. These are slow-growing cancerous tumours

Classification by location

Doctors also classify GEP-NETs based on where they develop in the digestive system^[3][9]:

• Foregut tumours form in the esophagus, stomach, upper part of the small intestine, liver, or pancreas
• Midgut tumours develop in the lower part of the small intestine, ascending colon, and first part of the transverse colon
• Hindgut tumours arise in the remaining parts of the colon and rectum

How common is this condition?

GEP-NETs are more common than many people realize. They are now more prevalent than some other tumours of the digestive tract, including stomach and pancreatic cancers combined^[3].

The number of people diagnosed with GEP-NETs has risen dramatically. This increase appears to be mainly due to finding more low-stage, low-grade disease, likely because of better detection methods^[12].

Causes and risk factors

Researchers do not know exactly what causes GEP-NETs to form. The tumours develop when neuroendocrine cells begin to divide and multiply out of control^[4].

Hereditary conditions

Most GEP-NETs occur by chance, but some are linked to inherited conditions. Having certain genetic syndromes increases the risk of developing these tumours^[3][10]:

• Multiple endocrine neoplasia type 1 (MEN1) is the most common hereditary syndrome associated with GEP-NETs. About 5% to 10% of people with insulinomas or glucagonomas also have MEN1
• Von Hippel-Lindau disease
• Neurofibromatosis type 1

Other risk factors

Certain conditions that affect stomach acid production may increase the risk of gastric NETs^[10]:

• Atrophic gastritis – when the stomach lining becomes thin
• Pernicious anemia – a condition affecting red blood cells
• Zollinger-Ellison syndrome – which causes the stomach to make too much acid

Signs and symptoms

Many GEP-NETs do not cause symptoms in the early stages. When symptoms appear, they vary depending on where the tumour is located and whether it releases hormones^[2][4][10].

Common symptoms

People with GEP-NETs may experience^[2][4]:

• Heartburn
• Weakness and fatigue
• Muscle cramps
• Indigestion
• Diarrhea
• Weight loss
• Skin rash
• Constipation
• Pain in the abdomen or back
• Yellowing of the skin and the whites of the eyes
• Dizziness
• Blurred vision
• Headaches
• Increased thirst and hunger
• Frequent urination

Carcinoid syndrome

Carcinoid syndrome may occur if the tumour spreads to the liver or other parts of the body. This condition causes a group of symptoms including uncomfortable flushing of the face and neck, wheezing, and severe diarrhea^[4][10].

Carcinoid syndrome happens when certain types of GEP-NETs release abnormal levels of serotonin, a hormone that helps regulate mood and many body functions^[5][11].

How doctors diagnose GEP-NETs

Diagnosing GEP-NETs often requires working with specialists from different medical fields. Doctors use several types of tests to find these tumours and understand how they are affecting the body^[3].

Physical examination and medical history

A healthcare provider will do a physical examination and ask about symptoms. They may ask when symptoms started and whether they are getting worse. They will also ask if anyone in the family has inherited disorders that increase the risk of GEP-NETs^[4].

Blood and urine tests

Blood tests can measure hormone levels, which may be very high if a tumour is releasing large amounts of hormones. These tests help doctors determine if a tumour is functional or nonfunctional^[4][10].

For functional pancreatic tumours, doctors may check^[13]:

• Fasting blood glucose and insulin levels for insulinomas
• Serum VIP for VIPomas
• Serum glucagon for glucagonomas
• Serum gastrin for gastrinomas

Imaging tests

Several imaging methods help doctors see where tumours are located and whether they have spread^[3][4][13]:

• Computed tomography (CT) scan of the abdomen
• Magnetic resonance imaging (MRI)
• Endoscopic ultrasound (EUS) – uses sound waves and a thin tube with a camera
• Endoscopic retrograde cholangiopancreatography (ERCP)
• Somatostatin receptor scintigraphy – a special scan that can detect neuroendocrine tumours
• Positron emission tomography (PET) scan

Endoscopy and biopsy

Doctors may use an endoscope – a thin, flexible tube with a camera – to look inside the digestive tract. During this procedure, they can take a small sample of tissue called a biopsy to examine under a microscope^[3][13].

Different types of endoscopy are used depending on where the tumour might be^[13]:

• Esophagogastroduodenoscopy (EGD) for the stomach and upper digestive tract
• Colonoscopy for the colon and rectum
• Bronchoscopy for lung tumours

Treatment approaches

Treatment for GEP-NETs depends on several factors, including the tumour’s location, size, grade, and whether it has spread. Because these tumours can be complex, treatment often involves a team of specialists working together^[3].

Surgery

Surgery is the main treatment when possible. Most patients receive surgery either alone or combined with other treatments^[12]. The goal is to remove the tumour completely. For tumours that have spread to the liver, doctors may use special surgical techniques or procedures to treat those areas^[3].

Medication therapies

Several types of medications can help treat GEP-NETs^[3][11]:

Somatostatin analogues are drugs that help control symptoms caused by hormone-releasing tumours. They work by blocking the release of certain hormones^[3].

Targeted biological agents include newer medications like sunitinib and everolimus. These drugs work differently than traditional chemotherapy by targeting specific parts of cancer cells. The addition of these therapies is most effective in high-stage, high-grade tumours^[3][11][12].

Chemotherapy uses drugs to kill cancer cells. Different chemotherapy combinations may be used depending on the type and grade of tumour^[3].

Radionuclide therapy

Radionuclide therapy uses radioactive substances attached to molecules that target neuroendocrine tumour cells. This treatment has had a significant impact on managing these diseases^[11].

Other treatments

Additional treatment options include^[3]:

• Radiological intervention – procedures that use imaging to guide treatment
• Radiation therapy – uses high-energy rays to kill cancer cells

Outlook and survival

The outlook for people with GEP-NETs varies greatly depending on several factors. These include the tumour’s location, stage when diagnosed, and grade (how fast the cells are growing)^[12].

Many GEP-NETs grow slowly and can often be controlled for many years. Some are curable^[10]. Research shows that patients with low-stage, low-grade disease have the longest survival, especially when tumours are in the small intestine or rectum^[12].

Recent studies have found an average survival of 27 years after diagnosis, though this varies significantly based on disease characteristics^[21].

Patients who undergo surgical removal of tumours generally have the best outcomes^[12]. Access to healthcare and socioeconomic factors also appear to affect survival. Having private insurance or Medicare, rather than Medicaid, and having higher income levels were associated with improved survival in recent studies^[12].

Living with GEP-NETs

Because GEP-NETs often grow slowly, people may live with them for many years. Doctors sometimes describe it as similar to managing a chronic illness^[21].

Diet and nutrition

Eating well is important for people with GEP-NETs. A balanced diet can help maintain strength and energy during treatment^[17][18].

Some people with functional tumours that cause carcinoid syndrome may find that certain foods trigger symptoms. Foods and drinks that may cause problems include^[14][17]:

• Aged or blue cheeses
• Chocolate
• Red wine and beer
• Smoked meats like salami or sausage
• Pickled fish
• Fermented foods like miso or sauerkraut

These foods are high in amines – compounds that can affect blood pressure or body temperature. Avoiding alcohol can help relieve skin flushing and is generally recommended since NETs often affect the liver^[17].

Other helpful diet tips include^[17][18]:

• Eating smaller, frequent meals throughout the day
• Avoiding fatty, greasy, or highly spicy foods
• Choosing whole, natural foods over processed ones
• Getting enough calories and protein, especially during chemotherapy

Working with a dietitian can help create an eating plan tailored to individual needs^[18].

Physical activity

Regular exercise can help people with GEP-NETs feel better overall. Taking a half-hour walk three times a week or more is a good way to stay active^[17][21].

Managing symptoms

Diarrhea can be a significant problem for some people with GEP-NETs. It is important to drink plenty of fluids – at least 2 to 3 litres a day – to replace what is lost. Eating small meals and snacks regularly can help. While high-fiber foods are usually healthy, they can make diarrhea worse. Instead, try foods like white rice, white pasta, well-cooked eggs, and white bread^[18].

For nausea and vomiting, eating light and bland foods such as plain toast and crackers may help. Anti-sickness drugs prescribed by a healthcare team can also provide relief^[18].

Emotional support

Living with GEP-NETs can be emotionally challenging. It is natural to feel anxious, stressed, frightened, or sometimes depressed^[15].

Building a support network can make a big difference. This might include^[15][21]:

• Talking with friends and family about how you feel
• Joining a support group for people with neuroendocrine tumours
• Meeting with a counsellor or therapist
• Trying stress management techniques like meditation

Many people find it helps to learn as much as they can about their condition. Information can make it easier to cope and make decisions. Making lists of questions before doctor appointments, bringing someone along to help remember what was said, and asking healthcare providers to explain things again if needed are all useful strategies^[15].

It is important not to let the disease control your life. Try to live as normally as possible and continue doing things you enjoy^[21].