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Neuroendocrine tumors are an insidious disease whose diagnosis is often too late. A disease in which up to every 25th cases are correctly diagnosed. The key to improving the situation is modern diagnostics and cooperation between doctors of different specialties.
Neuroendocrine tumors (NETs) are rare, atypical neoplasms that occur in 70% of cases in the digestive system1. They are diagnosed in 3-5 people out of 100 per year1. Due to non-specific symptoms (diarrhea, reddening of the skin, abdominal pain, muscle spasms)2 diagnostics are very delayed, even taking several years. Often, despite even a significant advancement of the disease, there is a possibility of treatment slowing the progression of the disease and improving the quality of life of patients. Cooperation between doctors of various specializations is necessary to improve the diagnosis and treatment of this disease.
Neuroendocrine tumors (NETs) are rare and atypical neoplasms whose cells are capable of producing, storing and secreting biogenic hormones and amines (biologically active “relatives” amino acids). These tumors develop from endocrine (endocrine) cells that are present in various parts of the body. NETs can occur in various organs and tissues, but 70% of them are located in the gastrointestinal tract1.
Neuroendocrine tumors can secrete hormonal compounds, which are then referred to as hormonally active. A significant proportion of these tumors do not produce enough hormones and / or biogenic amines to exhibit clinical symptoms, and are therefore called hormonally non-functional tumors. Depending on the substances secreted by NET tumors, we divide them into several groups:
— carcinoid tumors – the most common gastrointestinal pancreatic tumors. They account for half of all NET tumors1. In 90% of cases, they are malignant tumors, but the onset of the disease is asymptomatic. They originate in the small intestine, most often they are tumors of the appendix1. Their detection is most often accidental during surgical procedures for other reasons. Clinical symptoms, and thus the detection of a carcinoid tumor occurs when it is an advanced form of cancer and metastases appear. Carcinoid tumors secrete serotonin, which causes symptoms called “carcinoid syndrome” – reddening of the skin, diarrhea, difficulty breathing, asthma or wheezing, congestive heart failure, palpitations, abdominal pain, swelling1, 3.
— insulinoma – the second most common neuroendocrine tumor. It occurs in 17% of cases1. It produces insulin in an uncontrolled manner that can lead to severe hypoglycaemia3, i.e. a significant reduction in blood glucose levels. The most common symptoms are: headache and dizziness, disturbance in concentration, vision, speech, drowsiness, severe hunger, increased sweating, restlessness and irritability.3. About 30% of people experience significant weight gain3. Due to the non-specific and often periodic occurrence of symptoms, it is detected after several or even several years3.
— gastrinoma – occurs in 5% of NET cases1. It produces gastrin, which leads to the symptoms of persistent peptic ulcer disease3. Most often it appears as multiple nodules in the duodenal wall (40% of gastrinomas) or as a single tumor in the pancreas (40% of cases)3. In most cases, it is a malignant tumor. Excessive secretion of gastrin causes the following symptoms: persistent diarrhea, ulcers in unusual locations – esophagus, intestine3.
— glucagonoma – occurs in 2% of cases1. It is a glucagon-secreting tumor that occurs in the tail of the pancreas as a single, solid lesion, large (up to 25 cm)3. The first symptom of the disease may be hyperglycaemia3. In addition, the symptoms of glucagonoma are necrotic skin erythema, abdominal pain, nausea, diarrhea, rapid weight loss, anemia, deep vein thrombosis and pulmonary embolism.3.
— VIP’s – belongs to the rare neuroendocrine tumors (1%)1. Most often located in the pancreas or retroperitoneal tissue3. It secretes a vasoactive intestinal peptide (VIP) that causes a set of symptoms called pancreatic cholera. It is characterized by diarrhea with a significant loss of potassium and bicarbonate, hypokalemia (too little potassium) in the blood serum, and achloridia (no acid secretion)3.
— somatostatinoma – accounts for 1% of neuroendocrine tumors1. In the vast majority of cases (75%), a single tumor is located in the head of the pancreas3. It secretes somatostatin, a hormone that inhibits the secretion of digestive enzymes. The symptoms of the disease often include diarrhea, gallbladder enlargement, and calcium malabsorption disorders3.
Neuroendocrine tumors produce non-specific symptoms that may indicate many other diseases. Before a correct diagnosis is made, patients are often treated for other conditions – gastrointestinal ulcer, oversensitive intestine, asthma, lung cancer, and even alcoholism or mental illness. This is mainly due to the fact that NET tumors are very rare, and doctors who do not have daily contact with them in their offices do not suspect this tumor. Despite the increase in the detection of neuroendocrine tumors over the last 20 years, still too few are detected – 3-5 cases per 100 inhabitants1. Meanwhile, they occur more frequently. This is evidenced by autopsies during which neuroendocrine tumors are detected in 84 patients per 100 inhabitants.
Neuroendocrine tumors are often detected in the advanced stage, when they metastasize to the liver or lymph nodes. Therefore, an appropriate level of awareness and knowledge of doctors of various specializations (internists, gastroenterologists, surgeons, pathologists, endocrinologists, nuclear medicine doctors, oncologists) and their cooperation in order to improve the diagnosis and treatment of neuroendocrine tumors is crucial.
Due to the secretion of hormones, the basic diagnostic tool for neuroendocrine tumors is the determination of appropriate hormones in the blood.1. Patients are recommended to measure chromogranin A (CgA), 5-hydroxyindole acetic acid (5-HIAA), neuronspecific enolase (NSE) and synaptophysin)1. Imaging diagnostics is also of great importance, as it has improved significantly after the introduction of somatostatin receptor testing (the so-called scintigraphic examination – SRS) or positron emission tomography – PET – with the use of Gallium). About 80% of neuroendocrine tumors produce a characteristic protein on their surface – the somatostatin type 2 receptor. By administering to the patient a preparation that binds to this protein, it is possible to obtain an image of the tumor in the SRS or PET examination2,3. In the diagnosis of NET tumors, ultrasound with the use of an endoscope, computed tomography (CT) and magnetic resonance imaging (MR) are also used.4.
Treatment
Treatment of neuroendocrine tumors depends on the size of the tumor, its secretory functions and the presence of metastases. The treatment of choice is surgery, which allows the complete removal of the neoplasm2. For advanced lesions at diagnosis, surgery may not be possible. Then pharmacotherapy and chemotherapy are used2. First-line drugs are somatostatin analogues, and in the case of advanced or progressive disease, radioisotope therapy, interferon a, ablative therapy and chemotherapy are used.2. In recent years, new options for treating neuroendocrine tumors with the use of targeted therapies have emerged.
Literature:
1. Violetta Rosiek, Beata Kos-Kudła, “Neuroendocrine tumors – early diagnosis in primary health care”, Medycyna after Diploma, February 2013
2. Beata Kos-Kudła, Anna Zemczak, “Modern methods of diagnosis and treatment of neuroendocrine tumors of the digestive system” Endokrynologia Polska, Volume 57, number 2/2006, pp. 174-186
3. Marta Kunkel, “Gastrointestinal neuroedocrine tumors – characteristics, diagnosis, treatment”, Doctor’s Guide a 3/2005, pp. 107-113
4. Beata Kos-Kudła (ed) Neuroendocrine tumors of the digestive system. Gdańsk: Via Medica, 2010, pp 1-364