Pancreatic Neuroendocrine Tumour

Pancreatic neuroendocrine tumours are rare growths that start in special hormone-making cells inside the pancreas. Though uncommon, accounting for only 1 to 2% of pancreatic cancers, many of these tumours grow slowly and can be treated effectively, offering better outcomes than other types of pancreatic cancer.

Table of contents

• What are pancreatic neuroendocrine tumours?
• Other names for this condition
• Associated organs
• Types of pancreatic neuroendocrine tumours
• Signs and symptoms
• Causes and risk factors
• Possible complications
• How doctors diagnose the condition
• Treatment options
• Outlook and survival
• Living with pancreatic neuroendocrine tumours

What are pancreatic neuroendocrine tumours?

Pancreatic neuroendocrine tumours are growths that develop in the hormone-making cells (also called islet cells) of the pancreas^[1]. The pancreas is a long, flat organ about 6 inches in length that sits behind the stomach. It has three main sections: the head, the body, and the tail^[3].

The pancreas contains two types of cells. Endocrine cells make hormones such as insulin that help control blood sugar levels. These cells cluster together in small groups called islets throughout the pancreas. Exocrine cells make enzymes that are released into the small intestine to help digest food. Most of the pancreas consists of exocrine cells^[3].

Pancreatic neuroendocrine tumours start in the endocrine cells. These tumours may be benign (not cancer) or malignant (cancer). When they are malignant, they are sometimes called pancreatic endocrine cancer or islet cell carcinoma^[3].

These tumours are much less common than the usual type of pancreatic cancer, which starts in the exocrine cells. Only 1 or 2% of clinically significant pancreas growths are pancreatic neuroendocrine tumours^[5]. However, pancreatic neuroendocrine tumours generally have a better outlook than other types of pancreatic cancer^[3].

islet cell tumours, pancreatic endocrine tumours, PanNETs, PETs, PNETs

Other names for this condition

Pancreatic neuroendocrine tumours are known by several other names. They are often referred to as islet cell tumours because they arise from the islet cells in the pancreas^[5]. Doctors also call them pancreatic endocrine tumours or use the shortened terms PanNETs, PETs, or PNETs^[5][6].

Associated organs

• Pancreas
• Liver (when cancer spreads)
• Small intestine
• Stomach

Types of pancreatic neuroendocrine tumours

Pancreatic neuroendocrine tumours can be divided into two main groups based on whether they produce excess hormones. Functional tumours make large amounts of hormones that cause noticeable symptoms. Nonfunctional tumours do not produce excess hormones. Signs and symptoms from nonfunctional tumours happen as the tumour grows and spreads. Most nonfunctional tumours are malignant^[3].

Most pancreatic neuroendocrine tumours are functional tumours^[3]. There are several types of functional tumours, named according to the main hormone they produce:

Insulinomas are the most common type of functioning pancreatic neuroendocrine tumour. They release insulin, which is the hormone that keeps blood sugar from getting too high. About 10% of insulinomas are cancerous^[2].

Gastrinomas affect cells that release gastrin, which triggers the stomach to produce gastric acid. About 60% of gastrinomas are cancerous^[2]. When increased stomach acid, stomach ulcers, and diarrhoea are caused by a gastrinoma, the condition is called Zollinger-Ellison syndrome^[3].

Glucagonomas are often cancerous. They affect the cells that release glucagon, the hormone that keeps blood sugar from getting too low^[2].

VIPomas can be cancerous. “VIP” stands for “vasoactive intestinal peptide.” This hormone relaxes the muscles in the stomach and bowels and manages the balance of sugar, salt and water in the digestive tract^[2].

Somatostatinomas are slow-growing cancerous tumours that release somatostatin. This hormone manages several bodily functions^[2].

Signs and symptoms

Some pancreatic neuroendocrine tumours do not cause any symptoms. In such cases, they may be discovered by chance during a scan performed for a different reason^[5].

When symptoms do occur, they can include heartburn, weakness, fatigue, muscle cramps, indigestion, diarrhoea, 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, and increased thirst and hunger^[1].

Other common symptoms include severe acid reflux, loss of appetite, nausea and vomiting, frequent urination, uncomfortable flushing of the face and neck with wheezing, and unexplained weight loss. Some people experience big swings in blood sugar levels, either up or down^[2].

The specific symptoms depend on which type of tumour is present and which hormones are being produced in excess. For example, insulinomas cause symptoms of low blood sugar such as dizziness and weakness. Gastrinomas lead to stomach ulcers and severe diarrhoea. Glucagonomas can cause a distinctive skin rash, diabetes, and blood clots^[5].

Causes and risk factors

Researchers do not know the exact cause of pancreatic neuroendocrine tumours^[2]. However, some of these tumours occur alongside other conditions.

About 5% to 10% of people with insulinomas or glucagonomas also have a condition called multiple endocrine neoplasia type 1 (MEN1)^[2]. This is an inherited disorder that increases the risk of developing tumours in hormone-producing glands^[3].

Having certain inherited syndromes can increase the risk of pancreatic neuroendocrine tumours. Doctors may ask if anyone in your biological family has certain inherited disorders that raise the risk^[2].

Possible complications

The most significant complication of pancreatic neuroendocrine tumours is that cancerous forms can spread to other areas of the body. Without treatment, malignant tumours may spread to the bones, liver or lungs^[2].

How doctors diagnose the condition

A healthcare provider will perform 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 biological family has certain inherited disorders that increase the risk of pancreatic neuroendocrine tumours^[2].

Blood tests may show excess hormones or other signs of a pancreatic neuroendocrine tumour. Blood samples can also be used to look for changes in genetic material that signal an increased risk of these tumours. Urine tests may show breakdown products that occur when the body processes hormones^[8].

Imaging tests take pictures of the body to show the location and size of a pancreatic neuroendocrine tumour. Tests might include X-ray, MRI (magnetic resonance imaging), CT (computed tomography), and PET scan (positron emission tomography)^[8].

Doctors may perform imaging with nuclear medicine tests. These tests involve injecting a small amount of radioactive material into the body. The material sticks to pancreatic neuroendocrine tumours so that they show clearly on the images^[8].

During an endoscopic ultrasound, a thin, flexible tube with a camera on the tip is passed down the throat into the stomach and small intestine. The tube has a special ultrasound tool to create pictures of the pancreas. Other tools can be passed through the tube to collect a sample of tissue for examination^[8].

Providers use test results to determine if a tumour is functioning or non-functioning. Functioning tumours release unusually large amounts of hormones. Non-functioning tumours do not release excess hormones. Test results also help providers identify the specific type of pancreatic neuroendocrine tumour^[2].

Treatment options

Surgery is often the main treatment for pancreatic neuroendocrine tumours^[6]. The type of operation depends on where the tumour is located in the body. Surgery might be the only treatment needed, or it might be combined with other types of treatment. Doctors may recommend surgery even if the surgeon cannot completely remove the cancer. Removing part of the cancer can sometimes reduce symptoms. This is called debulking surgery^[6].

For people who have symptoms related to excessive hormone production, treatment may be needed straight away to help them feel better and to make sure they are well enough for surgery. This might include medications called somatostatin analogues, fluids through a drip if there has been severe diarrhoea, vitamin or mineral supplements, tube feeding if there has been significant weight loss, or pancreatic enzyme replacement therapy^[15].

Other treatment options include radiation therapy, chemotherapy, targeted cancer drugs, and a type of radioactive treatment called peptide receptor radionuclide therapy (PRRT). PRRT combines a targeting molecule that binds to specific receptors on tumour cells and a radioactive particle that destroys cancer cells. PRRT is given to patients through an intravenous infusion and has fewer side effects than other chemotherapies. A course of treatment typically includes four doses given eight weeks apart^[15].

Monthly injections of lanreotide, a drug that blocks the growth hormone that feeds these slow-developing tumours, may be used when surgery is not possible^[20].

Recently, a targeted therapy called cabozantinib has been approved for adults with a well-differentiated pancreatic neuroendocrine tumour who have received previous treatment, who are ineligible for surgery, and whose cancer has progressed^[13]. In clinical trials, patients who received this treatment had a median time of 13.8 months before their cancer worsened, compared to 3.3 months for those who did not receive it^[13].

Treatment decisions depend on the type of neuroendocrine tumour, how fast it is growing, how far the cancer has spread, and the patient’s general health and fitness. A team of doctors and other professionals discuss the best treatment and care for each person^[15].

Outlook and survival

Pancreatic neuroendocrine tumours generally have a better outlook than the more common type of pancreatic cancer. The five-year survival rate for a pancreatic neuroendocrine tumour is 95% if the tumour is localized and has not spread^[21].

Most pancreatic neuroendocrine tumours grow slowly. If they are localized and there is no evidence they have spread elsewhere, surgery will likely cure the cancer if caught in an early stage. Even if not cured, patients will often live a long time^[21].

Many pancreatic neuroendocrine tumours are benign, while some are malignant. The behaviour of an individual tumour can be unpredictable. Higher tumour grade, lymph node and liver spread, and larger tumour size generally indicate a less favourable outlook^[7].

The five-year relative survival rate for pancreatic neuroendocrine tumours that have spread is 23%, which highlights the need for new treatment options^[13].

Living with pancreatic neuroendocrine tumours

Living with a chronic disease like pancreatic neuroendocrine tumours can be challenging. Many people experience a range of emotions, including feeling shocked, upset, frightened, uncertain, confused, angry, guilty, or sad^[16].

Some people with pancreatic neuroendocrine tumours have a group of symptoms related to hormone overproduction. Certain foods and drinks may trigger problems like skin reddening, painful gas and bloating, and severe diarrhoea. Foods high in substances called amines—such as aged or blue cheeses, chocolate, red wine, beer, smoked meats, pickled fish, and fermented foods—may cause symptoms. Cutting back on wine and other alcoholic drinks can provide relief from skin flushing. Because these tumours tend to affect the liver, it is a good idea to avoid alcohol^[19].

Other helpful dietary approaches include eating smaller, frequent meals; avoiding fatty, greasy, or highly spicy foods; and choosing whole, natural foods over processed ones high in salt. Eating healthy foods can maintain strength and energy during treatment. If undergoing chemotherapy, it is important to get enough calories and protein^[19].

Maintaining an active lifestyle helps people feel better in general. Regular exercise, such as taking a half-hour walk three times a week or more, is beneficial. If someone smokes, quitting is important. Taking a multivitamin may help, as some people with pancreatic neuroendocrine tumours do not have enough of a nutrient called niacin, which can cause dry, cracking skin around the mouth^[19].

It is natural to feel anxious, stressed, and sometimes depressed when diagnosed with a pancreatic neuroendocrine tumour. Setting up a support network can help a great deal. Joining a support group for people who have these tumours can be beneficial. Meditation helps some people manage stress. Talking to a doctor or counsellor is important if help is needed dealing with emotional challenges^[19][16].

Talking to friends and relatives about the condition can provide help and support. Some people find it easier to talk to someone other than their own friends and family. Counselling can help cope better with the difficulties faced^[16].

Gathering information about the specific type of tumour and its treatment can help with coping and decision-making. Making lists, having a calendar with all appointments, setting goals, and planning enjoyable activities can all be helpful. Asking for help when needed is important^[16].