Diagnosis and Biomarkers

NETs may present a considerable diagnostic and therapeutic challenge as their clinical presentation is protean, non-specific and usually late when metastases are already evident. The classical carcinoid syndrome is relatively uncommon (10-15%), typically consisting of diarrhea, cutaneous flushing, bronchospasm and right-sided heart failure. Biochemical tests including plasma serotonin and 24-four hour measurement of urinary 5-hydroxyindole-3acetic acid (5-HIAA) in 5HT producing lesions. The general GI-NET marker plasma CgA levels are sensitive (>90%) but nonspecific (elevated in other types of NETs, impaired kidney function and during proton pump medication). Plasma serotonin levels are often unreliable and difficult to quantify, 5HIAA levels are cumbersome and insensitive while CgA levels vary between laboratories and can be non-specifically elevated. Topographic localization using CT, MRI, somatostatin receptor scintigraphy (SRS), whole body positron emission tomography (PET) or endoscopy/ultrasound are all variously effective depending upon equipment availability and user skill. No modality alone is entirely secure and overall exhibit a sensitivity specificity of ~ 80-90%.
A key unmet need is the availability of a blood test for early diagnosis or surveillance. The recent demonstration of specific NET transcripts in plasma suggests that this strategy may enable early diagnosis and detection such lesions and even provide a basis for prognostic determination and therapeutic recommendation.

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