Neuroendocrine cells are widely distributed in the human body, not only in some endocrine organs or tissues, but also in the bronchi and lungs, the gastrointestinal tract, the exocrine (ductal) system of the pancreas, the bile ducts, the liver, etc. This is known as the ‘diffuse neuroendocrine system’. In other words, neuroendocrine cells are present in many organs of the body, such as the lungs and gastrointestinal tract, and perform specific functions, such as regulating airflow through the lungs and blood, and controlling the speed of food passage through the digestive tract. Neuroendocrine tumors can occur in all organs and tissues of human body, but they are relatively common in endocrine organs, such as pituitary gland and adrenal gland, etc. Neuroendocrine tumors in non-endocrine organs are relatively common in lung, gastrointestinal tract and pancreas.
Compared with other types of tumors, the morphological variation of neuroendocrine tumors is relatively small. The general pathological and morphological manifestations of neuroendocrine tumors are that the tumor cells are often arranged in an organ-like pattern. The morphology of the tumor cells is more consistent and less interstitial. In short, most of these tumors have a relatively “benign” morphological presentation. “In the past, neuroendocrine tumors were thought to be rare, but with increased awareness, the identification of specific functional products and the application of relevant detection technologies, it has become apparent that these tumors are not rare or uncommon.
Early diagnosis is difficult
Neuroendocrine tumors are divided into carcinoid tumors and pancreatic endocrine tumors. Neuroendocrine tumors can be classified into two major categories – functional and non-functional – based on whether the substances secreted by the tumor cause typical clinical symptoms.
In the vast majority of patients with neuroendocrine tumors, there are no typical symptoms in the early stage, so early diagnosis of such tumors is difficult. Only a very small number of patients with gastrointestinal neuroendocrine tumors have early symptoms, for example, carcinoid tumors will have sudden or persistent skin flushing on the head, face, and trunk; occurring in the stomach, they will be accompanied by abdominal pain, diarrhea, and also recurrent peptic ulcers; and occurring in the pancreatic area, the characteristic manifestation is neurogenic hypoglycemia, which commonly occurs in the early morning or after exercise, and other manifestations include blurred vision and abnormal behavior.
”Patients with non-functional disease have no previous symptoms, and most of them receive attention only after physical examination reveals a mass or tumor metastasis, and are diagnosed clearly by histopathology.” When non-functioning neuroendocrine tumors are diagnosed, they are often already at an advanced stage, and 65% of patients with advanced gastroenteropancreatic neuroendocrine tumors have an overall survival of no more than five years. Therefore, according to Jia Liqun, early diagnosis is crucial to the treatment of neuroendocrine tumors.
No distinction between the old and the young in getting the disease
Last year, many media claimed that Steve Jobs, the “Godfather of Apple”, died of pancreatic cancer. In fact, according to the findings published by the American media, Jobs had a neuroendocrine tumor, but it happened to be located on the islet cells of the pancreas, not pancreatic cancer. Jobs said thankfully before his death, “The remaining life of a pancreatic cancer patient is usually very short, and very fortunately, what I had was not pancreatic cancer.”
Islet cell tumors are neuroendocrine tumors, while pancreatic cancer is an adenocarcinoma of the digestive system. There is a big difference in that islet cells are scattered in the pancreas to secrete hormones such as insulin and glucagon, and its function is to regulate a person’s blood sugar. In contrast, the glands in pancreatic cancer mainly secrete fluid, which is involved in digestion and breakdown of food through digestive juices, etc.
Pancreatic neuroendocrine tumors have been considered to be of low incidence, only 1.4% of tumors of exocrine glandular origin of the pancreas, and have a better prognosis than pancreatic cancer. Clinically, tumors localized in the pancreas are benign and can be resolved by surgical resection; however, if they are metastatic, multiple, or advanced, it is difficult to cure them.
The lesions of neuroendocrine tumors are not necessarily in islet cells, other organs like adrenal cortex and pituitary gland may become cancerous, they are collectively called neuroendocrine tumors, and adults and children may become patients.
Chromogranin A can predict the disease
Early diagnosis of neuroendocrine tumors is very difficult. 2007 International Congress of Neuroendocrine Tumor Specialists in Washington, D.C. noted that all types of neuroendocrine tumors are far more prevalent than various rare cancers, yet they receive far less attention than cancer.
The diagnosis of neuroendocrine tumors is divided into qualitative diagnosis (detection of specific levels of abnormally secreted hormones) and local diagnosis (various imaging tests). Chromogranin A (CgA) level is a specific indicator of neuroendocrine tumors and is the most commonly used qualitative diagnosis in clinical practice.
If it belongs to a non-functional neuroendocrine tumor, it is impossible to extract a good prognosis, but at present, the most helpful diagnostic tool for the disease is the non-specific marker chromogranin A in blood, which increases by 60-100% in almost all patients except insulinomas. Chromogranin A levels are positively correlated with tumor severity, and changes in blood chromogranin A levels precede imaging changes.
The change of blood chromogranin A level is earlier than the imaging change, so it can play a predictive role for the development and regression of tumor.
Imaging is the main method to localize the diagnosis and also to monitor the response during the treatment. PET is more sensitive than CT and MRI for early diagnosis of tumors. The sensitivity of growth inhibitory receptor imaging varies depending on the type of tumor, with gastroenteropancreatic neuroendocrine tumors having a higher sensitivity.
Early treatment has a higher 5-year survival rate.
If functional tumors are detected early by professional doctors and operated early, the five-year survival rate after surgery can reach more than 70%-80%; if non-functional, most of them are found with physical examination, in this case metastasis has already occurred, and clinically this type of patients often come to the clinic with symptoms related to metastatic lesions, which is not effective.
For the treatment of neuroendocrine tumors, the treatment strategy differs in different sites, stages of disease and pathological grading. As the pathogenesis of this type of disease is not fully understood, surgery is the main means to obtain radical cure for this type of tumor, while systemic combination therapy, such as chemotherapy and molecular targeted therapy, is the main treatment for those patients with advanced combined metastases. “Each treatment modality has its own advantages and disadvantages, and the choice of treatment should be determined according to the actual situation of the patient, including the simultaneous or sequential application of multiple modalities.”
First, surgical resection is the only radical means of treatment for neuroendocrine tumors. For patients who can be surgically resected, the 5-year survival rate can reach 80-100%. However, most tumors develop distant metastases, and achieving complete resection is clinically beneficial for patients with metastases. For neuroendocrine tumors with liver metastases, surgery can reduce the tumor load and prolong survival. Clinically, chemotherapy is mostly the first-line treatment option for inoperable moderate-to-low-proliferative advanced pancreatic neuroendocrine tumors.
Secondly, biological therapies are mainly growth inhibitor analogues, such as long-acting octreotide, which can reduce tumor secretion and inhibit tumor growth by promoting apoptosis and arresting the cell cycle.