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.
What Are Gastrointestinal Neuroendocrine Tumors, Gastrointestinal Carcinoid Tumors and Gastrinomas?
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.
Risk Factors for Gastrointestinal Neuroendocrine Tumors and Genetics
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.
Signs of a Gastrointestinal Neuroendocrine Tumor
Gastrointestinal NET symptoms may occur because the tumor releases the hormones serotonin (most common) or gastrin. Symptoms can also come from the tumor growing or turning cancerous and spreading.
High Serotonin Levels
When GI carcinoids make and release serotonin, the liver usually processes the extra amount, with no impact on the body. But if the disease spreads to the liver, the organ can’t keep up. In fact, metastases in the liver may release even more serotonin.
High serotonin levels cause a condition called carcinoid syndrome, with about 40 percent of GI carcinoids triggering this complication. These carcinoids are most commonly found in the small intestine, the appendix and the start of the colon. Symptoms of carcinoid syndrome include:
- Diarrhea
- Flushing (warmth and redness in the face)
- Wheezing (a whistling sound when breathing becomes difficult)
Effects from Gastrin Hormone
Another GI NET, gastrinoma, can cause different symptoms by releasing the hormone gastrin. Individuals with this tumor experience:
- Diarrhea
- Steatorrhea (oily stools)
- Peptic ulcers (painful sores on the lining of the stomach or small intestine)
Tumor Growth, Location and Spread
Other signs of a GI NET come from the tumor reaching a large size, blocking the GI tract or interfering with the liver. They include:
- Belly pain
- Constipation
- Fatigue
- Jaundice (yellowing of skin or eyes)
- Nausea and vomiting
- Rash
- Red or particularly dark stool from intestinal bleeding
- Unexplained weight loss
Diagnosing Gastrointestinal Neuroendocrine Tumors
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 (learn more about nuclear medicine for neuroendocrine tumors)
Why Choose the Abramson Cancer Center for a Gastrointestinal NET?
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. Learn more about neuroendocrine tumor research and clinical trials.
- 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.
How We Treat Gastrointestinal Neuroendocrine Tumors
Everyone we treat receives personalized recommendations after a thorough review by our tumor board. We develop the proposed plan based on:
- Tumor size and rate of growth
- Whether the tumor is releasing hormones and, if so, what kind
- Whether cancer has spread and how extensively
- If the liver is involved and how much disease it contains
- Your symptoms
- Your preferences and overall health
Surgery for GI NETs
Whenever possible, we recommend neuroendocrine tumor surgery to remove or reduce tumors. Our surgeons can often remove GI NETs that are benign (noncancerous) but still need treatment as well as malignant (cancerous) tumors that have not spread too widely. In either case, our surgeons may take a minimally invasive approach, with a shorter hospital stay and faster recovery.
Even if we can’t remove all the cancer, surgery can still play an important role:
- Removing the primary tumor: When the disease has spread, we believe taking out the original tumor still helps. Not all programs take this approach. However, we feel removing the primary tumor has benefited because it:
- stops the primary tumor from blocking the GI tract
- decreases the risk of developing localized complications
- lessens the number of hormones released
- may prevent further metastases
- Identifying the NET: Sometimes, imaging can’t find small primary tumors. Surgery can help determine if someone actually has a GI neuroendocrine tumor or a pancreatic neuroendocrine tumor.
- Debulking: With larger primary GI tumors, debulking (reducing their size) can be beneficial.
- Treating the liver: Surgery is the first option for metastatic disease in the liver. Removing at least 90 percent of any disease in the liver can essentially set the clock back 10 years in terms of how cancer has grown.
Therapies for GI NETs With More Disease or Spread
Many people eventually need multiple therapies, potentially spread over many years. Options include:
- Medications: Somatostatin analogs are drugs that mimic the hormone somatostatin. They are typically the first treatment tried for carcinoids, as they can control cancer growth and relieve symptoms tied to hormone release. Another type of medication, targeted therapy, interferes with the ways carcinoids grow, but doesn’t effectively manage symptoms from hormone release. Learn more about drug therapy for neuroendocrine tumors.
- Liver therapy: When there’s too much liver disease for surgery, other treatments can shrink tumors quickly and effectively. Learn more about liver-directed therapy for neuroendocrine tumors.
- Clinical trials: We develop new medications and other treatments through clinical trials and may have one that fits your needs. Learn more about neuroendocrine tumor research and clinical trials.
- Peptide receptor radionuclide therapy (PRRT): We deliver targeted radiation using a molecule specifically geared toward GI carcinoid cells. Radiation therapy can stop cancer from progressing for a number of years. Learn more about nuclear medicine for neuroendocrine tumors and PRRT.
- Radiation therapy: Radiation given by a machine outside the body can treat metastatic sites in the bones and lungs. Learn more about radiation therapy.
- Chemotherapy: For poorly differentiated tumors — the NECS — certain drugs treat cancerous cells across the body. Learn more about chemotherapy.
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