Gastrointestinal neuroendocrine tumors

When neuroendocrine tumors form in the gastrointestinal (GI) tract, the most effective care comes from a program used to seeing these complex cases. At Penn Medicine, our team regularly treats a range of GI NETs, from those releasing hormones to those with liver disease.

We’re known and respected for treating gastrointestinal neuroendocrine tumors with our surgeries, development of new therapies and support for quality of life. For diseases we can’t fully remove, we provide effective management and symptom control, always looking to your future.

Gastrointestinal neuroendocrine tumors (GI NETs) are a type of neuroendocrine tumor that develops within the GI tract, anywhere from the esophagus to the anus. Most often, they form in the small intestine (small bowel) or mesentery, the tissue securing the intestines to the belly’s wall. Another frequent location is the rectum, the last section of the large intestine (large bowel).

While various types of neuroendocrine tumors can occur throughout the body, they form most frequently in the GI tract.

Doctors distinguish gastrointestinal neuroendocrine tumors by their:

• Frequency: With roughly 8,000 people in the U.S. diagnosed a year, GI NETs are fairly rare. But they’re still the second-most common GI tumor after colorectal cancer.
• Hormone potential: Most GI NETs are carcinoids, which can release certain hormones and lead to symptoms. (GI carcinoids are also called carcinoids of the alimentary, or digestive, tract.) Another, uncommon type of GI NET called gastrinoma,releases a different hormone.
• Behavior: Like other neuroendocrine tumors, most GI carcinoids grow slowly. They often metastasize (spread) but it may take years. The most common locations of metastatic GI carcinoids are the lymph nodes and liver, followed by the bones and lungs. While tumors can spread when fairly small, they can also grow quite large before doing so.
• Appearance: The cells of GI carcinoids look like normal cells (well-differentiated). The cells of a much less common NET, GI neuroendocrine carcinoma, appear very different. These poorly differentiated tumors, also called NECs, act more aggressively and pose a greater treatment challenge.

Doctors typically don’t know why a GI NET forms. They have identified one possible risk factor for stomach NETs — diseases that reduce stomach acid.

In a small number of cases, a genetic change, or variant, inherited from a parent leads to a GI NET. Variants of either of these genes raise the risk for particular tumors:

• MEN1: These variants lead to multiple endocrine neoplasia type 1, or MEN1. People with the condition are much more likely to develop a range of tumors, including gastrinoma in the duodenum, the small intestine’s first section. They’re also at higher risk for lung neuroendocrine tumors and pancreatic neuroendocrine tumors.
• NF1: These variants cause neurofibromatosis type 1, or NF1. The condition features an increased risk of a GI carcinoid in the duodenum. People with NF1 can also develop an adrenal gland NET called a pheochromocytoma.

Learn more about our genetic testing for neuroendocrine tumors, and our genetic counseling.

There are three main scenarios that lead to a GI NET diagnosis:

• You may feel the effects of hormone release.
• You may experience symptoms of tumor growth or spread.
• A tumor might be found during surgery or imaging for another GI condition.

Because GI NETs grow slowly, symptoms may not appear right away. And when they do, they overlap with other conditions. For these reasons, diagnosing GI NETs can be challenging. Most people are diagnosed between the ages of 55 and 65, and many have diseases that’s spread to the liver.

At Penn, we can help with all types of cases. Our thorough evaluation may include:

• CT and MRI of the belly and pelvis
• Endoscopy (examination with thin tubes with lights and cameras) of the GI tract, along with biopsy when needed
• Needle biopsy if still needed, to analyze tumor cells to see if they are well-differentiated and how fast they’re dividing and multiplying
• Urine tests to measure serotonin over 24 hours
• Blood tests for chromogranin A (CgA), a protein released by NETs, or gastrin
• PET/CT imaging, either specially tailored for NETs or more general for aggressive cancers

Care for GI neuroendocrine tumors is complex. To get an accurate diagnosis and effective, individualized treatment that minimizes side effects, you need a knowledgeable team.

Our program brings together a range of specialists with expertise in these tumors. Each team member brings years of experience and an understanding of the nuances particular to GI NETs. When you seek our care, you’ll find:

Coordination: For the best GI NET care, you need providers who collaborate. Each week, our specialists meet to discuss cases and agree on the best next steps. Learn more about our Neuroendocrine Tumor Program, including our tumor board.

Expertise: Our specialists focus on GI NETs, publishing papers and developing new treatments. They also help craft national treatment guidelines and participate in national working groups dedicated to research and improved care. A few examples of where the expertise of our neuroendocrine tumor team comes into play:

• • Many GI NETs grow slowly. But sometimes disease expands a little more quickly (grade 2 tumor) or even turns aggressive (grade 3). Our team can make the challenging distinction between the later grades and identify appropriate therapy.
  • Even with a metastatic GI NET, the disease typically doesn’t move quickly. Effective treatment depends on pacing and therapy sequencing. Rushing can introduce harm. We draw on the evidence — both from studies and what we’ve seen before.
  • GI NETs often spread to the liver, a particularly critical organ. But the severity varies, and other areas might benefit from treatment first. Our team determines if the disease is mostly in the liver (liver dominant) and what needs are most pressing to protect your health.

Options: We offer a full range of treatments, including liver-directed therapy and nuclear medicine. We also conduct research and develop new therapies. In fact, we ran the trial that led to the first nuclear medicine approval for GI NETs.

Support: At our program, a nurse navigator helps with appointment scheduling and many other needs. We also provide GI symptom management for neuroendocrine tumors — diarrhea control is a frequent concern — and other ways to support neuroendocrine tumors.