Shedding light on pancreatic neuroendocrine tumors

Understanding neuroendocrine tumors. Neuroendocrine cells are found throughout the body, particularly in the small bowel, pancreas, stomach, adrenal glands, lungs, and thyroid. When these cells received messages from the nervous system, they release hormones. Neuroendocrine tumors, or NETs, are tumors that form in neuroendocrine cells.

NETs are rare and complex. Because their behavior can be difficult to predict, it is important for patients to be seen by an experienced team of doctors for diagnosis and treatment. The NETs care team at University of Chicago Medicine includes experts across many specialties.

They work together to accurately diagnose neuroendocrine tumors, and to determine the most effective treatment for each patient. At UChicago Medicine, treatment for NETs often includes surgery, even for tumors that have spread to other organs.

Our surgeons are some of the most experienced in the country at treating NETs, and to use unique state of the art techniques to destroy and remove tumors. In addition, we were one of the first centers in the country to offer a promising treatment called Peptide Receptor Radionuclide Therapy, or PRRT.

PRRT combines a targeting molecule that binds to specific receptors on tumor cells and a radioactive particle that destroys cancer cells. PRRT is given to patients through an IV infusion, and has fewer side effects than other chemotherapies. A course of treatment typically includes four doses given eight weeks apart.

At UChicago Medicine, our researchers are working to find the underlying cause of these tumors, and to bring new treatments, including innovative clinical trials, for the most challenging cases. Want to learn more about treatment and the newest clinical trials for neuroendocrine tumors? UChicago Medicine is here to help. Visit
Pancreatic cancer has been in the national spotlight lately with “Jeopardy” host Alex Trebek revealing his diagnosis. For the majority of all pancreatic cancer cases, the cancer begins in the ducts of the pancreas. This is known as pancreatic ductal adenocarcinoma and is the deadliest form of the disease. The other 5%-10% fall under the category of pancreatic neuroendocrine tumors (pNETs). While rare form, pNETS are still potentially deadly. Two prominent people who succumbed to pNETs include Aretha Franklin and Steve Jobs.

To learn more about pNETs and how they differ from other types of pancreatic cancer, we spoke with Xavier Keutgen, MD, the director of University of Chicago Neuroendocrine Tumor Program and one of the few surgeons in the country with advanced expertise in extensive removal of neuroendocrine tumors. Keutgen is also a lead investigator on several clinical trials focusing on new diagnostic and therapeutic methods for endocrine and neuroendocrine tumors.
Neuroendocrine tumors are tumors that develop from neuroendocrine cells. These are cells that can be found in almost every organ in the body yet, despite the word “neuro,” they have nothing to do with the brain. Their name stems from the cells’ connection to the autonomic nervous system (the nervous system that you cannot control). Neuroendocrine tumors can develop in any organ that has neuroendocrine cells. These cells produce hormones or proteins that can be secreted in our bloodstream. For example, in the pancreas, you can find these cells in pancreatic islets, which secrete hormones like insulin that regulate our blood sugar. Although pancreatic neuroendocrine tumors develop from these islet cells that normally secrete hormones, about 75% of the tumors are nonfunctional and do not produce hormones.
Currently, 170,000 people live with a NET tumor in the United States. Each year, 400-700 people in the Chicagoland area are diagnosed with a neuroendocrine tumor. It’s not as rare as most people think and is even getting more common. That's most likely due to a combination of being able to better diagnose these tumors and just a general increase in occurrence. I think that, overall, the most common NETs we see in a clinical setting at UChicago Medicine are NETs of the lung, small bowel and pancreas.
The most common mistake is that “pancreatic cancer” is confused with “pancreatic neuroendocrine tumors.” Usually pancreatic cancer is defined as adenocarcinoma of the pancreas (derived from pancreatic ductal cells), which has a bad prognosis. Only 5% to 10% of pancreatic tumors are pNETs. They behave differently, have a much better prognosis and are treated completely differently. Unlike the more common type of pancreatic cancer, 50% of patients that have metastasized pNET (or cancer that has spread to other parts of the body) live five years or longer after diagnosis.
The most common treatment is surgery. If the tumor is still localized and has not spread, we remove tumors greater than 2 centimeters. We recently published a study examining the correlation between tumor size and surgery and what size is best to perform surgery for. If the tumor secretes hormones (~10-25% of patients), the tumor is resected regardless of size. If the tumor has spread, surgery is still common. Here at UChicago Medicine, we are very good at and specialized in this type of surgery.

For example, if the tumor has spread to the liver, we can remove the primary tumor from the pancreas, while also taking out all or almost all of the disease in the liver with very specialized techniques to prevent harm to the remaining sections of healthy liver. This is called parenchymal-sparing resection, which allows us to take out parts of the tumor carefully, one-by-one. The deeper tumors can be burned with microwave ablation. With this technique, we can resect 30, 40 or sometimes up to 50 lesions out of the liver without damaging liver function. 
Unlike adenocarcinoma, classic chemotherapy is rarely used to treat pNETs. In addition to or instead of surgery, some patients received intramuscular injections or a daily oral pill to slow down the tumor growth, which sometimes is successful for many years. Recent, more advanced therapies include the new and promising PRRT therapy, or peptide receptor radionuclide therapy. PRRT is a radioactive infusion given every other month for eight months that targets the tumor cells without having to affect other organs. It has minimal side effects and is a promising therapy because it can shrink the tumor in up to 30-40% of patients with pancreatic neuroendocrine tumors.
Since most tumors do not secrete hormones, most patients are asymptomatic. That means they have no obvious symptoms like weight loss and abdominal pain. They also don't turn yellow (jaundice). These tumors grow slowly over months and years without ever being noticed. In many cases, the patients may get a CT scan or ultrasound for another condition, which is how their tumor is found. If the tumors do secrete hormones such as insulin or gastrin, they are typically diagnosed more quickly. That's because they can cause hypoglycemia, leading to low glucose levels and passing out or lead to stomach acidity and ulcers.
There are some rare inherited genetic conditions that make some people more susceptible to having NETs. Besides rare genetic syndromes, we do not currently know of a reason why people develop these tumors.
Here at UChicago Medicine Comprehensive Cancer Center, my laboratory focuses on understanding why some people respond better to certain therapies than others. We are studying how to improve the effectiveness of PRRT to make it better for pancreatic and other NET patients. We also specialize in trying combination therapies, such as combining PRRT with surgery. Also, next year, we will be starting a clinical trial specifically examining these combination therapies for patients with pancreatic neuroendocrine tumors.
Xavier M. Keutgen, MD, FACS

Xavier M. Keutgen, MD, FACS

Xavier M. Keutgen, MD, is a surgical oncologist with particular expertise in treating neuroendocrine, thyroid, parathyroid and adrenal tumors. Dr. Keutgen is the director of the UChicago Medicine Neuroendocrine Tumor Center and works closely with multidisciplinary team that specializes in NETs.

Read Dr. Keutgen's physician profile.