Neuroendocrine tumors are a heterogeneous group of neoplasms originating from the diffuse endocrine system. Depending on primary location and hormonal status, they range in terms of clinical presentation, prognosis and treatment. Functional tumors often develop symptoms indicating an excess of hormones produced by the neoplasm (exempli gratia insulinoma, glucagonoma and VIPoma) and can be diagnosed using monoanalytes. For non-functional tumors (inactive or producing insignificant amounts of hormones), universal biomarkers have not been established. The matter remains an important unmet need in the field of neuroendocrine tumors. Substances researched over the years, such as chromogranin A and neuron-specific enolase, lack the desired sensitivity and specificity. In recent years, the potential use of Circulating Tumor Cells or multianalytes such as a circulating microRNA and NETest have been widely discussed. They offer superior diagnostic parameters in comparison to traditional biomarkers and depict disease status in a more comprehensive way. Despite a lot of promise, no international standards have yet been developed regarding their routine use and clinical application. In this literature review, we describe the analytes used over the years and cover novel biomarkers that could find a use in the future. We discuss their pros and cons while showcasing recent advances in the field of neuroendocrine tumor biomarkers.

IntroductionOver the years, pulmonary carcinoids have been treated as locally malignant tumors because of the favorable prognosis. It is currently known that the clinical course of the disease is mainly dependent on the carcinoid subtype.AimTo analyze the early and long-term surgical treatment outcomes for typical and atypical carcinoids.Material and methodsA total of 90 patients were treated surgically for pulmonary carcinoid tumors in the years 2007–2015. Typical carcinoids were diagnosed in 69 (77%) cases, while atypical carcinoids – in 21 (23%); 67 patients underwent lobectomy, 3 – sleeve lobectomy, 9 – bilobectomy, 2 – pneumonectomy, 1 – segmentectomy, and 8 – wedge resection.ResultsNone of the patients died in the postoperative period. Complications occurred in 14.4% of patients. The most common complications included: arrhythmias (5.6%), prolonged air leak (3.3%), and residual pneumothorax (3.3%). Among the 21 patients with atypical carcinoids, N1 metastasis was found in 1 (4.8%) patient, while N2 – in 5 (23.8%) patients. In the group of 69 patients with typical carcinoids, N1 metastasis was revealed in 7 (10.1%) patients and N2 metastases – in 2 (2.9%) patients. The probability of 5-year survival in patients with typical and atypical carcinoids was 96% and 83%, respectively. During the follow-up period 7 (7.8%) patients, including 6 with atypical carcinoids, experienced local recurrence; distant metastasis occurred in 8 (8.9%) cases, including 6 with atypical carcinoids.ConclusionsAlthough radical surgical treatment provides excellent long-term outcomes, it should be noted that patients with pulmonary carcinoids (especially with the atypical subtype) may experience local recurrence and distant metastases even many years after surgery.

Introduction: Neuroendocrine tumors (NETs) are rare neoplasms that occur in various locations throughout the body. Despite their usually benign character, they might manifest with distant metastases. N-terminal prohormone of brain natriuretic peptide (NT-proBNP) has previously been described as a useful biomarker in diagnosing carcinoid heart disease (CHD), a common advanced NETs manifestation. We observed plasma concentrations of NT-proBNP in metastatic midgut NETs over a 4-year period. Objectives: We aimed to explore NT-proBNP concentrations in states of varying levels of cell proliferation and disease status. Our goal was to investigate NT-proBNP’s role in predicting disease progression in relation to previous research and up-to-date scientific guidelines. Patients and methods: We performed a retrospective multivariate analysis of NT-proBNP concentrations in 41 midgut NETs patients treated with somatostatin analogs, all with liver metastases. NT-proBNP concentrations were measured in every patient across 16 evenly distanced time points over a 48-month period and were compared to variables such as sex, age, grading, Ki-67, primary tumor location, and CT findings. Results: NT-proBNP concentrations correlated positively with higher liver tumor burden, higher grading, high Ki-67 levels, and with progressive disease in CT. There were no differences in NT-proBNP levels with regard to primary location (ileum vs jejunum), sex, and age. Conclusion: We conclude that NT-proBNP is a useful analyte for monitoring NETs progression, due to its increased concentration in scenarios implying increased cellular proliferation. These long-term follow-up results align with previous findings and suggest an additional role for NT-proBNP in diagnostic algorithms, beyond a carcinoid heart disease biomarker.

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