The included NEN patients were subjected to baseline biochemical work-up as well as cross-sectional and functional imaging with somatostatin receptor scintigraphy or 68- Gallium-PET/CT at diagnosis, whereas those already followed, i.e., patients with residual or recurrent disease post-surgery and those with distant-stage disease were monitored with CT or MRI at varying time intervals, as per ENETS guidelines and clinically indicated per patient [21,22]. During these visits, follow-up laboratory tests with concurrent sampling of urine and serum 5-HIAA were obtained prospectively along with kidney function tests. Renal function tests were considered abnormal, when plasma-Creatinine concentration was >100 μmol/L and/or eGFR was <50 mL/min/1.73 m2. Serum 5HIAA was measured within 3 months of a CT/MRI in patients undergoing at least 2 sequential examinations within a period of 1–24 months. Patients were instructed to avoid foods rich in serotonin that would interfere with 5-HIAA measurement 3 days prior to and during sample collection. Drugs that could potentially affect metabolism of serotonin and thus the 5-HIAA test were also discontinued. CT/MRI followed standardized NEN examination protocols [23]. Morphological imaging of the abdomen (CT or MRI) was further reviewed, and the highest liver tumor load (LTL) was recorded. The following staging system was used to describe the stage of liver involvement: stage 1 =< 5 metastases confined in 1 lobe, stage 2 = bilobar and/or 5–10 metastases, and stage 3 => 10 metastases or diffuse metastatic disease.

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