Neuroendocrine tumors (NETs) are unusual and very difficult to diagnose. They develop slowly with non-specific symptoms that can easily be confused with other diseases. Before an appropriate diagnosis is made, many patients are suspected of, for example, gastrointestinal ulcer disease, asthma, menopausal symptoms, and even neurosis.
Knowledge about neuroendocrine tumors is still insufficient, which means that the diagnosis of the disease takes up to 52 months on average! On the other hand, what distinguishes this neoplasm from others is the fact that even late detection, in the spreading stage, can be effectively treated.
Neuroendocrine tumors, shortly called NETs (neuroendocrine tumors), are relatively rare and very specific neoplasms – they can develop in the patient’s body for years without showing any characteristic symptoms or imitating symptoms of completely different diseases. This means that before patients suffering from neuroendocrine neoplasm receive the correct diagnosis, they seek help from various specialists for many years. They treat asthma, peptic ulcer disease, inflammation of the intestines, irritable bowel syndrome, and mature women often ignore the symptoms when they suspect they are experiencing menopause. Meanwhile, the cancer is progressing.
Neuroendocrine neoplasms can be divided into secreting and non-secreting neoplasms, there are many more of the latter. Of all pancreatic neuroendocrine neoplasms, hormonally inactive tumors account for 60-90%. Secreting tumors, otherwise hormonally active, produce certain hormones or substances responsible for the occurrence of more or less characteristic symptoms. For example, if the tumor produces insulin, symptoms associated with lowering blood sugar, such as increased heart rate, increased sweating, hunger, nervousness, and sometimes even disturbances in consciousness that may lead to loss of consciousness appear.
Sometimes these are diarrhea, hot flushes, reddening of the skin, abdominal pain, which are so nonspecific symptoms that they are not associated with the possibility of a neuroendocrine neoplasm. Unfortunately, most neuroendocrine neoplasms do not produce the hormones that produce the typical symptoms, and they do not appear until tumor metastasis occurs.
It is also worth paying attention to the fact that the symptoms of the disease may not be repeatable, appear for some time and then completely disappear, which means that often patients and doctors ignore them. All this is the reason for visiting a specialist late. And the disease gradually progresses – explains prof. dr hab. n. med. Alicja Hubalewska-Dydejczyk, endocrinologist, Head of the Clinical Department of Endocrinology at the University Hospital in Krakow.
Due to the lack of characteristic symptoms or symptoms suggesting other diseases, neuroendocrine neoplasms are often diagnosed at random.
– Performing screening tests such as gastroscopy, colonoscopy or even an ultrasound of the abdominal cavity may completely accidentally reveal the presence of a polyp, asymptomatic tumor, or even tumor metastases. If a neuroendocrine neoplasm is suspected, the most sensitive diagnostic method is the examination of somatostatin receptors. It is based on the presence of these receptors on the surface of cancer cells. By administering to the patient an analog of a protein expressed on the cell surface and combining it with an appropriate radioactive isotope, it is possible to recognize the location of a neuroendocrine tumor, determine its advancement, qualify the patient for targeted treatment, and monitor its effectiveness, as well as the course of the disease. Due to the lack of characteristic symptoms, the diagnosis of NET often takes 5-7 years. Sometimes the symptoms are so uncharacteristic, for example erythematous lesions, ulcerations on the skin, that the patient first sees a dermatologist, and in the absence of other symptoms, no one will think that it may be a neuroendocrine neoplasm. Unfortunately, late diagnosis of the disease is also a consequence of the persistently insufficient knowledge about NETs among physicians and patients. It turns out that over 50% of patients have never heard of neuroendocrine neoplasms, which is why educating both doctors and the public is so important. The biggest challenge in the diagnosis of NETs is to detect the disease when it does not yet show any characteristic symptoms, hence the importance of screening and responding to various initial symptoms of the disease, and this is possible only when you think about the fact that some non-specific ailments are a neuroendocrine tumor may become – emphasizes prof. Sun dr hab. n. med. Anna Sowa-Staszczak, specialist in the field of endocrinology, internal medicine and nuclear medicine.
NET TUMORS – WHAT SYMPTOMS MAY INDICATE THE DISEASE?
The ambiguity in the assessment of neuroendocrine tumors makes them very difficult to diagnose even for a number of experienced doctors of various specialties. Patients with their atypical symptoms report, inter alia, to to cardiologists, pulmonologists, gastrologists and allergists. However, there are symptoms whose regular, long-term repetition may signal the presence of cancer. These include symptoms that mimic irritable bowel syndrome, asthma-like symptoms, paroxysmal reddening of the skin, difficulty breathing, muscle spasms, swelling, and unexplained anxiety.
– Among the so-called tumors are secreting tumors that produce serotonin, which can, especially in the presence of metastatic lesions, give symptoms of the so-called carcinoid syndrome, which includes: diarrhea, flushing, cramping abdominal pain, asthma-like symptoms associated with bronchospasm, such as coughing and shortness of breath, sometimes muscle weakness, dysfunction of the heart valves, edema and myocardial fibrosis. Other secreting tumors are located in the pancreas. These include the insulin-producing tumor mentioned earlier, a glucagon-producing tumor that may develop diarrhea, carbohydrate disturbances, erythema migrans skin lesions, and a gastrin producing tumor showing symptoms of recurrent ulcer disease with abdominal pain, weight loss body, diarrhea and anemia or anemia. Other pancreatic tumors called somatostatinomas or VIPomas are very rare. On the other hand, non-secreting tumors may give symptoms related to a growing tumor, pressure on adjacent organs, such as diarrhea, abdominal pain, jaundice. Sometimes there may even be gastrointestinal obstruction, which is the first symptom of the disease. It should be remembered that 70% of neuroendocrine neoplasms are located within the gastrointestinal tract. Other locations may include the lungs, head and neck structures, the genitourinary system, and even the mammary glands. Unfortunately, the first symptoms of the disease are easy to miss, especially when they appear sporadically. A signal that should not be underestimated is the repeatability of symptoms, their recurrence, the appearance of new, often unusual, e.g. changes on the skin, accompanied by diarrhea, and the appearance of symptoms suddenly, with a tendency to intensify quickly, suggesting, for example, obstruction of the duct alimentary tract. In such cases, a specialist consultation is necessary, often starting with a general practitioner who should direct the patient to the right specialist, explains Prof. Alicja Hubalewska-Dydejczyk.
DIAGNOSIS AND WHAT’S NEXT?
What distinguishes neuroendocrine tumors from other neoplasms is the fact that they grow much more slowly, thus giving a much better prognosis. In the case of neuroendocrine neoplasms, even late detection of the disease does not exclude the chance for effective treatment. As emphasized by dr hab. Anna Sowa-Staszczak, prof. The Jagiellonian University is good news, considering that almost 60 percent of In patients, the disease is diagnosed at an advanced stage with metastases to other organs.
– Most of the neuroendocrine neoplasms are slowly growing neoplasms with low growth dynamics, which, despite the advancement of the disease, enable the normal functioning of patients for many years. Unfortunately, this is not a rule, sometimes the spread of the disease may be associated with shortening the survival to several months. The average survival time in the case of locally advanced disease is 10 years, with distant metastases it is shortened. Such a long-term course of neuroendocrine neoplasms, combined with a good general condition, distinguishes neuroendocrine neoplasms from other neoplasms. Surgery is the first line of treatment that is always being sought. In the event of radical removal of the tumor, the patient remains under observation. If the disease is advanced at the time of diagnosis and metastases are present, surgical treatment is aimed at removing the primary tumor, which may slow down the disease dynamics or reduce the tumor mass, which may reduce the symptoms of the disease. If the treatment is not radical and the tumor remains after a diagnostic test with a somatostatin analogue, which is aimed at determining whether there are places on the tumor surface to which the given compound will attach, the so-called a somatostatin analogue. In the case of disease progression, it is possible to administer a therapy based on the addition of a radioactive isotope to the somatostatin analog, called targeted therapy. During treatment with somatostatin analogues, diarrhea, abdominal pain, constipation, and sometimes high blood glucose levels occur occasionally. Treatment with isotope-combined somatostatin analogues is associated with a greater number of complications, mainly related to a decrease in the level of leukocytes or platelets, and renal failure. However, they still account for a lower percentage of side effects of therapy than in the case of classic chemotherapy. Chemotherapy for NETs is used less frequently, unless the disease is progressing very rapidly. It is worth emphasizing, however, that despite the good prognosis of some neuroendocrine tumors and the slow course of the disease in most of them, the disease must be detected as soon as possible, and therefore its possible symptoms should not be ignored, says Prof. Anna Sowa-Staszczak.
WHERE TO TREAT NET TUMORS IN THE MAŁOPOLSKIE VOIVODSHIP?
The Endocrinology Clinic of the University Hospital in Krakow has been dealing with patients with NET since the 2000s. Initially, patients came here mainly with secreting tumors due to their characteristic symptoms. In non-secreting tumors, largely due to the lack of diagnostic criteria and the possibility of their histopathological identification, they were classified as classic gastrointestinal neoplasms or disseminated neoplasms with no known primary site. Introducing a wider use of the so-called receptor scintigraphy with somatostatin analogues (initially in a research project in XNUMX, and then for routine diagnostics), the possibility of determining disease markers and improving histopathological diagnostics, resulted in a significant increase in the diagnosis of the disease.
Currently, over 800 patients remain under the care of the Clinic’s Clinic every year, about 150 new people come to the clinic every year. Most of the patients from the Małopolskie voivodship with confirmed, mainly highly differentiated NET, remain under the care of the Clinic. The clinic also consults patients from other parts of Poland. About 20 percent. patients are patients who require oncological treatment who are under the control of Oncology Clinics.
The team of the Endocrinology Clinic dealing with the management of patients with NET consists of endocrinologists, nuclear medicine specialists and oncologists. Moreover, surgeons, radiologists and pathologists participate in multidisciplinary councils.
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