Gastroenteropancreatic neuroendocrine tumour disease is a rare and complex group of cancers that develop from hormone-producing cells in the digestive system and pancreas, often growing slowly over many years and presenting unique challenges in diagnosis and treatment.

Understanding Gastroenteropancreatic Neuroendocrine Tumours

Gastroenteropancreatic neuroendocrine tumours, often shortened to GEP-NETs, are uncommon cancers that start in special cells scattered throughout the digestive system and pancreas. These cells are called neuroendocrine cells, which work like a combination of nerve cells and hormone-making cells. They produce hormones that help control digestion and manage blood sugar levels^[2].

These tumours can develop anywhere along the gastrointestinal tract, from the stomach to the rectum, and in the pancreas. The disease is sometimes called by other names, including carcinoid tumours or islet cell tumours, depending on where they form^[3][5].

What makes GEP-NETs particularly challenging is their varied nature. Some tumours release extra hormones into the bloodstream, causing specific symptoms. These are called functional tumours. Other tumours, known as nonfunctional tumours, do not produce excess hormones but can still cause problems as they grow and affect nearby organs^[5].

Epidemiology: How Common Are These Tumours

Although GEP-NETs were once considered extremely rare, the number of people being diagnosed has increased dramatically over recent decades. Data from the United States shows a remarkable rise of more than 400 percent in the incidence of this disease over a 29-year period, climbing from 1.09 cases per 100,000 people in 1973 to 5.25 cases per 100,000 people in 2004^[3].

This increase is likely not because more people are developing the disease, but rather because doctors have better tools to find these tumours. Improved imaging techniques like CT scans and more widespread use of procedures such as colonoscopy and endoscopy mean that tumours are being detected that might have gone unnoticed in the past^[12].

Recent data suggests that GEP-NETs now represent about 6.33 percent of all cancers affecting the digestive system and pancreas. Interestingly, they are more common than some other well-known cancers, including stomach and pancreatic adenocarcinomas combined^[3][12].

People are typically diagnosed with GEP-NETs in their fifth decade of life, meaning most patients are in their 40s or 50s when they discover they have the disease. The condition is generally younger at diagnosis compared to other gastrointestinal cancers^[3].

Causes and Origins

The exact cause of gastroenteropancreatic neuroendocrine tumours remains unclear. Scientists know that GEP-NETs form when neuroendocrine cells begin to divide and multiply in an uncontrolled way, eventually forming tumours that can affect the organs where these cells are located. However, what triggers this abnormal cell growth is not yet understood^[4].

Most GEP-NETs occur spontaneously, meaning they happen without any obvious trigger or inherited condition. However, in some cases, these tumours can be linked to rare genetic syndromes that run in families. These inherited conditions involve changes, or mutations, in certain genes that control cell growth^[3].

Unlike infectious diseases, GEP-NETs are not contagious and cannot be transmitted from one person to another. They develop from changes within a person’s own cells rather than from any outside organism or pathogen.

Risk Factors: Who Is More Likely to Develop GEP-NETs

Several factors can increase a person’s risk of developing gastroenteropancreatic neuroendocrine tumours. Understanding these risk factors can help both doctors and patients recognize who might be more vulnerable to the disease.

Having a family history of certain rare inherited syndromes significantly increases the risk of GEP-NETs. One of the most important is multiple endocrine neoplasia type 1, or MEN1, which causes tumours to form in various hormone-producing glands. About 5 to 10 percent of people with specific types of pancreatic NETs also have MEN1^[4][10].

Other hereditary conditions that increase risk include Von Hippel-Lindau disease and neurofibromatosis type 1. These genetic syndromes can predispose individuals to developing multiple neuroendocrine tumours over their lifetime^[3][11].

Certain stomach conditions also raise the risk of developing GEP-NETs in the digestive system. These include conditions that affect the stomach’s ability to produce acid, such as atrophic gastritis, pernicious anemia, or Zollinger-Ellison syndrome. When the stomach cannot make enough acid, it can lead to changes in the cells lining the stomach, potentially increasing cancer risk^[10].

It’s important to remember that having one or more risk factors does not mean a person will definitely develop GEP-NETs. Many people with these risk factors never develop the disease, while others without any known risk factors do. If you believe you might be at increased risk because of family history or other factors, discussing this with your doctor can help determine whether any monitoring or testing might be appropriate.

Symptoms: How GEP-NETs Affect the Body

The symptoms of gastroenteropancreatic neuroendocrine tumours vary considerably depending on where the tumour is located and whether it produces excess hormones. Many people with GEP-NETs have no symptoms at all in the early stages, and their tumours are discovered only incidentally during tests for other conditions^[10].

When symptoms do appear, they can be vague and easily mistaken for more common, less serious conditions. Common symptoms include persistent diarrhea, which can be severe and disruptive to daily life. People may also experience ongoing fatigue that doesn’t improve with rest, unexplained weight loss even when eating normally, and loss of appetite^[2][4].

Digestive problems are frequent, including heartburn, indigestion, nausea, and vomiting. Some people develop pain in the abdomen or back. Constipation can occur, alternating with or instead of diarrhea. These symptoms happen because the tumours can interfere with normal digestion and the movement of food through the intestines^[2].

When tumours produce excess hormones, they cause additional specific symptoms. Some people experience uncomfortable flushing of the face and neck, where the skin suddenly becomes red and feels warm. Wheezing and other breathing difficulties may occur. These symptoms are part of a condition called carcinoid syndrome, which happens when certain hormones like serotonin are released into the bloodstream in large amounts^[4][5].

Pancreatic NETs can cause symptoms related to blood sugar problems. People might experience weakness, frequent urination, increased thirst and hunger, dizziness, blurred vision, and headaches. These occur when tumours affect insulin, glucagon, or other hormones that control blood sugar levels^[2][4].

Some individuals develop yellowing of the skin and the whites of the eyes, a condition called jaundice. This happens when a tumour blocks the bile ducts or affects liver function. Muscle cramps and skin rashes may also appear in certain types of GEP-NETs^[2].

Prevention: Can GEP-NETs Be Prevented

Unfortunately, there are no proven ways to prevent gastroenteropancreatic neuroendocrine tumours because the exact causes of these tumours are not well understood. Unlike some other cancers where lifestyle changes can reduce risk, GEP-NETs do not have clear links to behaviors such as smoking, diet, or alcohol use that can be modified^[3].

For people with inherited genetic syndromes that increase GEP-NET risk, such as multiple endocrine neoplasia type 1 or Von Hippel-Lindau disease, genetic counseling and testing can be valuable. If you have a family history of these conditions, speaking with a genetic counselor can help you understand your risk and determine whether testing for family members might be appropriate^[10].

Regular medical monitoring may be recommended for people with known genetic syndromes that increase NET risk. This surveillance typically involves periodic blood tests and imaging studies to detect tumours early when they are most treatable. While this doesn’t prevent the tumours from forming, it can catch them at an earlier, more manageable stage.

For stomach NETs specifically, managing conditions that affect stomach acid production, such as chronic atrophic gastritis, might help reduce risk. However, more research is needed to confirm whether treating these conditions actually prevents NET development^[10].

Because early detection improves outcomes, being aware of symptoms and seeking medical attention for persistent digestive problems or other concerning symptoms is important. While this doesn’t prevent the disease, it can lead to earlier diagnosis and treatment.

Pathophysiology: What Happens in the Body

To understand how gastroenteropancreatic neuroendocrine tumours affect the body, it helps to know what neuroendocrine cells normally do. These cells are scattered throughout the digestive system and pancreas, where they make and release hormones that help control various bodily functions. These hormones regulate digestion, blood sugar levels, and the movement of food through the intestines^[10].

When GEP-NETs develop, the normal control mechanisms that limit cell growth break down. The neuroendocrine cells begin dividing uncontrollably, forming a mass or tumour. Because these cells come from hormone-producing tissue, many tumours retain the ability to make and release hormones, sometimes in much larger quantities than normal cells would produce^[2].

The tumours are classified based on their origin within the digestive system. Foregut tumours develop in the esophagus, stomach, first part of the small intestine, liver, or pancreas. Midgut tumours form in the second part of the small intestine, the end of the small intestine called the ileum, the jejunum, and the beginning portions of the colon. Hindgut tumours arise in the lower colon and rectum^[3][11].

Each location tends to produce different patterns of hormone release and symptoms. Midgut tumours, for example, often produce serotonin, a hormone that affects mood and many body functions. When large amounts of serotonin enter the bloodstream, it can cause flushing, diarrhea, and other symptoms of carcinoid syndrome. These tumours are generally slow-growing but have a high tendency to spread to other parts of the body^[11].

Pancreatic NETs can produce various hormones depending on which type of cell in the pancreas becomes cancerous. Insulinomas make too much insulin, causing dangerously low blood sugar. Gastrinomas produce excess gastrin, leading to too much stomach acid and resulting in painful ulcers. Glucagonomas make too much glucagon, which raises blood sugar levels. Each of these functional tumours creates its own specific set of problems in the body^[2][4].

As GEP-NETs grow, they can cause mechanical problems in addition to hormone-related symptoms. Large tumours may block the intestines or bile ducts, preventing normal flow of food or digestive fluids. Tumours in the pancreas can interfere with the production of enzymes needed for digestion. When NETs spread to other organs, particularly the liver, they can affect liver function and cause additional complications^[4].

The behavior of GEP-NETs varies considerably. Most grow slowly, taking many years to develop and spread. However, some tumours are more aggressive and can grow and spread more rapidly. The speed of growth and the tendency to spread are influenced by factors including the tumour’s grade, which measures how abnormal the cells look under a microscope and how quickly they are dividing^[3][12].

When tumours do spread beyond their original location, they most commonly travel to nearby lymph nodes first, then to the liver, and sometimes to bones or lungs. This process, called metastasis, occurs when cancer cells break away from the original tumour, travel through the bloodstream or lymphatic system, and establish new tumours in other parts of the body^[4].