Small bowel neuroendocrine tumors (SBNETs) are cancers originating from specialized hormone-producing neuroendocrine cells found throughout the body. Although relatively rare, SBNETs are the most common malignancy occurring within the small intestine. These tumors are defined by their unique ability to secrete hormones, which gives rise to distinct clinical features. SBNETs often behave differently from other gastrointestinal cancers, requiring specific management strategies.
The Nature of Small Bowel Neuroendocrine Tumors
SBNETs primarily arise from enterochromaffin cells lining the small intestine. They are characterized as well-differentiated neuroendocrine tumors (NETs), meaning their cells closely resemble the normal cells from which they originated. SBNETs are typically slow-growing compared to aggressive adenocarcinomas, often delaying the onset of noticeable symptoms.
The biological behavior of SBNETs is categorized by their ability to secrete hormones, classifying them as either “functional” or “non-functional.” A tumor is considered functional if it secretes enough hormones or vasoactive substances, such as serotonin, to cause a distinct set of symptoms.
The tumor’s grade significantly influences prognosis and treatment planning. Grading is determined by the Ki-67 proliferation index, which measures how quickly the cells are dividing. Well-differentiated tumors are divided into Grade 1 (slow-growing) and Grade 2 (moderately growing). Poorly differentiated, high-grade tumors are termed neuroendocrine carcinomas (NECs) and require a different, more aggressive treatment approach. SBNETs are most commonly G1 or G2.
Recognizing Symptoms and Confirming Diagnosis
The initial symptoms of SBNETs are often vague, leading to a significant delay in diagnosis. Non-specific symptoms include chronic, intermittent abdominal pain, fatigue, and changes in bowel habits. As the tumor grows, it can physically constrict the small intestine, leading to symptoms of partial bowel obstruction.
A more specific presentation is Carcinoid Syndrome, which occurs when the tumor releases excessive hormones directly into the bloodstream. Classic symptoms include facial flushing, chronic watery diarrhea, and occasionally wheezing or difficulty breathing. In advanced cases, high levels of serotonin can lead to Carcinoid Heart Disease, characterized by the thickening and damage of heart valves.
Diagnosis relies on a combination of biochemical markers and specialized imaging. Blood tests often measure Chromogranin A (CgA), a protein co-secreted by neuroendocrine cells. A more specific test, particularly for those causing Carcinoid Syndrome, is the 24-hour urine collection for 5-HIAA (5-hydroxyindoleacetic acid), the primary breakdown product of serotonin.
Initial anatomical imaging typically involves CT or MRI scans of the abdomen and pelvis. However, the most sensitive method for staging is the \({}^{68}\)Ga-DOTATATE PET/CT scan. This test uses a radioactive tracer that binds to somatostatin receptors (SSTRs) on the tumor cells, guiding treatment decisions for targeted therapies.
Current Management and Treatment Strategies
The management of SBNETs is complex. Treatment decisions are tailored based on the tumor’s grade, the extent of its spread (stage), and the presence of Carcinoid Syndrome symptoms.
For tumors confined to the small bowel or regional lymph nodes, surgical resection is the primary curative treatment option. The procedure typically involves removing the primary tumor, associated lymph nodes, and surrounding mesentery. Even when the cancer has spread to the liver (metastatic disease), surgery to remove the primary tumor is often recommended to prevent complications like bowel obstruction.
Systemic treatments control tumor growth and manage symptoms in patients with metastatic disease. Somatostatin Analogs (SSAs), such as Octreotide or Lanreotide, are often the first-line medical therapy. These medications bind to the SSTRs on the tumor cells, reducing hormone secretion and stabilizing tumor growth.
Another highly targeted approach is Peptide Receptor Radionuclide Therapy (PRRT), often using \({}^{177}\)Lu-DOTATATE. This treatment links a somatostatin analog to a therapeutic radioactive particle. Once injected, the molecule travels directly to the tumor cells, binds to the SSTRs, and delivers a highly localized dose of radiation. For patients with higher-grade tumors (G3) or those that are SSTR-negative, cytotoxic chemotherapy, such as capecitabine and temozolomide, may be the preferred option.
Life After Treatment: Monitoring and Outlook
Following successful treatment, patients with SBNETs require long-term surveillance. The follow-up schedule is individualized based on the tumor’s initial grade and stage. For completely resected, well-differentiated tumors, surveillance typically involves regular imaging and biomarker checks.
Imaging, such as CT or MRI, and biochemical markers like CgA and 5-HIAA are monitored at regular intervals. The goal of this follow-up is to detect any recurrence early.
The long-term outlook for SBNETs is generally more favorable than for many other gastrointestinal cancers. The median overall survival for small intestinal NETs is reported to be many years, with five-year survival rates often exceeding 70%. Prognosis is heavily dependent on the tumor’s grade and whether the disease was localized or had already spread to distant sites at the time of diagnosis.