Abstract
In patients with gastroenteric and pancreatic neuroendocrine neoplasms (GEP-NENs), the risk of liver metastases is high, but the accuracy of standard imaging for detecting small hepatic nodules is limited. This raises concerns about the adequacy of staging in cM0 patients. This study aims to determine the percentage of cM0 GEP-NEN patients with occult liver metastases that can be identified using intraoperative ultrasound (IOUS) during surgery for the primary tumor. A prospective study was conducted at three high-volume centers between October 2020 and December 2023. Patients who underwent surgery for GEP-NENs staged as cM0 based on CT and PET/CT (MRI in selected cases) were included. IOUS was systematically performed, in combination with contrast-enhanced IOUS (CE-IOUS) and biopsy when necessary. The ground truth was the result of a contrast-enhanced CT or MRI performed 6 months after surgery. A total of 51 cM0 GEP-NEN patients were enrolled. IOUS detected suspicious liver nodules in seven patients (14%). Three were classified as metastatic based on the IOUS pattern, CE-IOUS pattern, and biopsy, respectively, while four were classified as non-metastatic based on biopsy (n = 2) or CE-IOUS pattern (n = 2). At six-month follow-up imaging, two patients (4%) were confirmed as metastatic (the suspicious metastasis at CE-IOUS was not confirmed). GEP-NENs G3 and those with necrosis had a higher risk of metastases (one-third of patients, p < 0.05 compared to G1-2 and non-necrotic neoplasms). IOUS, combined with CE-IOUS and biopsy, achieved 100% sensitivity, 98% accuracy, and 100% negative predictive value. IOUS, along with CE-IOUS and biopsy, provides accurate staging in GEP-NENs, identifying occult metastases in approximately 4% of cM0 cases. Due to the low incidence of occult metastases, routine use of IOUS cannot be recommended. It should be considered selectively in aggressive tumors, which have shown a significantly higher risk of liver involvement.