What is Pancreatic Islet Cell Cancer?
The pancreas is a body part that looks like a thin pear on its side, positioned behind the stomach and in front of the backbone. It has four sections: the head (the wider part), the neck, the body (middle section), and the tail (narrow end).
The pancreas has two types of cells – endocrine and exocrine. The endocrine cells release hormones like insulin and glucagon, that help regulate blood sugar levels. Small groups of these endocrine cells in the pancreas are also known as islets.
Exocrine cells, on the other hand, release hormones into the small intestine to help digest food. These cells are situated along the ends of ducts running through the pancreas.
Sometimes, tumors can grow in the pancreas or nearby areas. If these tumors originate from neuroendocrine cells (cells that release hormones into the bloodstream), they are referred to as pancreatic neuroendocrine tumors or islet cell tumors of the pancreas.
What Causes Pancreatic Islet Cell Cancer?
In most instances, pancreatic neuroendocrine tumors, which are a type of tumor that starts in the pancreas, occur on their own. But sometimes, they can be part of a condition known as multiple endocrine neoplasia type 1, which also involves tumors in the parathyroid and the front part of the pituitary gland. This disease happens when a gene called Menin, located in the DNA strand on chromosome 11q13, stops working. Menin gene is what we call a ‘tumor suppressor gene’, meaning it usually helps control the growth of cells and prevents tumors.
When these pancreatic tumors show up as part of multiple endocrine neoplasia type 1, it’s possible to get more than one tumor in the pancreas. They can also be part of other diseases, like von Hippel Lindau disease (a genetic condition that can cause tumors and cysts in the body), neurofibromatosis type 1 (a disorder characterized by skin changes and growth of noncancerous tumors), and tuberous sclerosis (a condition that causes the growth of noncancerous tumors in many parts of the body).
Risk Factors and Frequency for Pancreatic Islet Cell Cancer
Research shows that the rate of neuroendocrine tumors has significantly increased over time. In fact, from 1973 to 2012, the number of cases multiplied by nearly six times, from 1.09 to 6.98 cases per 100,000 people. Specifically, the gastropancreatic sites were most affected, with a rate of 3.56 cases per 100,000 people. As for the United States, in 2014, the recorded number of cases over a 20-year period was around 171,321.
On a hopeful note, the overall survival rates for all neuroendocrine tumors have been improving over time. Notably, the survival rate for advanced stage pancreatic neuroendocrine tumors saw a significant increase when comparing the periods 2000-2004 and 2009-2012.
- The incidence of neuroendocrine tumors has increased roughly six-fold from 1973 to 2012, reaching 6.98 cases per 100,000 people.
- The highest rate of these tumors was found in the gastropancreatic sites, with 3.56 cases per 100,000 people.
- As of January 1, 2014, the total number of cases over 20 years in the United States was reported to be 171,321.
- The overall survival rates for all neuroendocrine tumors has been on the rise. This is particularly notable for advanced-stage pancreatic neuroendocrine tumors, with a significant improvement seen between the periods of 2000-2004 and 2009-2012.
Signs and Symptoms of Pancreatic Islet Cell Cancer
Non-functional pancreatic neuroendocrine tumors often aren’t detected until later stages, when they’ve grown large or spread because the symptoms they cause are typically a result of their size rather than their function. Symptoms could include yellowing of the skin or eyes (jaundice), back pain, diarrhea, indigestion, abdominal pain, or feeling a lump in the abdomen.
Functional pancreatic neuroendocrine tumors, on the other hand, cause different symptoms based on the specific type.
- Gastrinomas — tumors that release a substance called gastrin — typically present with peptic ulcers and diarrhea. Sometimes, these ulcers can be multiple or resistant to treatment, leading doctors to suspect a gastrinoma.
- Insulinomas often cause too much insulin production, leading to low blood sugar. These symptoms, combined with other symptoms of low blood sugar that improve after eating, are known as the Whipple triad.
- VIPomas cause a condition known as VIPoma syndrome or WDHA syndrome, which includes watery diarrhea, low potassium levels, and a lack of stomach acid.
- Glucagonomas can lead to a condition known as glucagonoma syndrome, featuring weight loss, anemia, diabetes, blood clots, mental symptoms, and digestive disturbances. They can also cause a specific type of rash known as necrolytic migratory erythema.
- Carcinoid tumors typically lead to carcinoid syndrome, which includes skin flushing, heart valve disease, and diarrhea. These symptoms are caused by serotonin, which is produced by the tumor.
It’s also worth noting that even though most of these tumors metastasize to the liver, it is possible for them to develop without spreading to the liver. Furthermore, the absence of carcinoid syndrome doesn’t necessarily rule out carcinoid tumors of the pancreas.
Testing for Pancreatic Islet Cell Cancer
Pancreatic neuroendocrine tumors (PNETs) can be complicated to diagnose, often leading to delays in identifying the condition. The main goal of diagnosis is to understand the type of PNETs, the severity, and location of primary and secondary growths, and whether the tumor is producing hormones or not.
Tests that measure hormone levels can play a significant role in diagnosing the tumor, especially if functional PNETs are suspected. These tests might still be recommended even without clear signs of a disorder caused by too much hormone production. This is because the patient may have elevated hormone levels that aren’t causing noticeable symptoms. In such cases, these hormones can be used as markers in later evaluations. There are several markers for PNET, including Chromogranin A (CGA), neuron-specific enolase (NSE), and a hormone called pancreastatin. Doctors might also measure fasting levels of other hormones produced by functional PNETs, such as pancreatic polypeptide, glucagon, gastrin, insulin, vasoactive intestinal polypeptide, and proinsulin.
Imaging tests such as magnetic resonance imaging (MRI) or computed tomography (CT) scans of the abdomen and pelvis can help assess any potential metastases or spread to the liver, pancreas, and lymph nodes. Another type of imaging using a substance called octreotide can help determine the tumor’s affinity for a hormone called somatostatin, and it can also detect tumors that might be missed by other imaging methods. Tissue samples for a biopsy can be taken from liver masses using ultrasound or CT guidance. If a sample of a pancreatic mass is needed, endoscopic ultrasound guidance may be used. The biopsy helps identify the tumor type and grade, as well as aiding in immunocytochemical staining for hormones.
For a type of PNET known as carcinoid tumors in the pancreas, confirmation is based on imaging tests and at least one of the following needs to be present: Elevated levels of a substance called 5-hydroxyindoleacetic acid in the urine, or detection of a hormone called 5-hydroxytryptamine in the tissue sample or its elevation in the blood.
Treatment Options for Pancreatic Islet Cell Cancer
Pancreatic islet cell cancers are often slow-growing, but a proactive approach is usually recommended over adopting a “wait-and-see” approach. This aggressive approach includes removing the main and spread-out (metastatic) tumors. Implementing this strategy requires a team of specialists to provide care before and after surgery.
The ideal solution for a non-spread-out (non-metastatic) primary tumor of the pancreas is to remove it surgically. If the cancer has spread to the liver, surgically reducing the size of these tumors (debulking) is an important treatment strategy. This helps to lower the amount of hormones the tumor is producing as well as to lessen the physical impact of the tumor itself.
To treat pancreatic liver metastasis, different techniques can be used such as microwave ablation, bland embolization, chemoembolization, radiofrequency ablation, radioactive polymer microspheres, and transcutaneous alcohol ablation. These procedures help to target and destroy the tumors in the liver.
It is common for patients to still have some trace of the disease even after they have received surgical and localised treatments due to the stubborn nature of these tumors. Those patients will need systemic therapy to manage any remaining tumors. Functional pancreatic tumors, such as VIPoma and glucagonoma, can be managed effectively at this stage with drugs that mimic the hormone somatostatin (somatostatin analogs) such as octreotide, lanreotide, and pasireotide. However, the use of these drugs in treating nonfunctional pancreatic tumors is still a topic of ongoing discussion.
What else can Pancreatic Islet Cell Cancer be?
Images of pancreatic neuroendocrine tumors can sometimes look like images of other conditions, which can make it tricky to diagnose them correctly. The conditions that can appear similar include:
- Acinar cell carcinoma of the pancreas
- Solid pseudopapillary neoplasm of the pancreas
- Pancreatoblastoma
To confirm the diagnosis, doctors rely on a biopsy of the affected area. This is the most reliable way to identify pancreatic neuroendocrine tumors.
What to expect with Pancreatic Islet Cell Cancer
Pancreatic neuroendocrine tumors usually have a better chance of recovery compared to pancreatic adenocarcinomas, a type of pancreatic cancer. However, if the tumor has spread to other organs or if the entire tumor could not be surgically removed, the chances of recovery might be lower. Furthermore, functional pancreatic endocrine tumors, which are tumors that produce hormones, typically have a better prognosis compared to non-functional ones, which do not produce hormones.
Possible Complications When Diagnosed with Pancreatic Islet Cell Cancer
Complications can sometimes occur due to tumors, either from the hormones they release or due to their size. These complications can include recurring inflammation of the pancreas, blockage of the intestine, and internal bleeding caused by the tumor itself. One serious complication could even be the development of swollen blood vessels due to a tumor obstructing the blood supply from the spleen.
There’s also a specific condition associated with tumors, known as Carcinoid syndrome. This condition can cause a severe complication called a Carcinoid crisis, which results in symptoms such as sudden confusion, flushing, excessive body heat, irregular heartbeats, diarrhea, inability to breathe normally, and significant changes in blood pressure. This complication can be triggered by various factors such as imaging procedures, chemotherapy, anesthesia, surgery, stress, or even simple examination of the tumor area.
Patients usually receive medication known as ‘somatostatin analogs’ to both treat and prevent a Carcinoid crisis from happening. However, the effectiveness of these medications in such scenarios is currently a topic of debate.
Common Complications:
- Recurrent pancreatitis
- Intestinal obstruction
- Internal bleeding
- Swollen blood vessels due to obstruction of blood supply
- Carcinoid crisis with multiple severe symptoms
Treatment and Prevention:
- Somatostatin Analogs
Preventing Pancreatic Islet Cell Cancer
There aren’t any specific environmental factors that increase or decrease the likelihood of developing pancreatic neuroendocrine tumors, a type of tumor that forms in the hormone-making cells of the pancreas. However, people with certain genetic conditions are at a higher risk of developing these tumors. These conditions include multiple endocrine neoplasia type 1 (it causes tumors to grow in endocrine glands), Von Hippel Lindau syndrome (it causes tumors and cysts to grow in the body), neurofibromatosis type 1 (it causes skin and nerve tumors), and tuberous sclerosis (it leads to noncancerous tumors in different parts of the body such as the brain, kidneys, and heart).
It’s important for people with these diseases to know that they have a higher chance of developing pancreatic neuroendocrine tumors. By being aware of this risk and the symptoms of these tumors, these individuals can seek medical help early in the course of the disease. Early intervention can help manage the disease and potentially limit tumor progression.
