Mixed neuroendocrine non-neuroendocrine neoplasms constitute rare tumors that are located mainly in the gastrointestinal (GI) tract and have high degrees of malignancy, and the frequency of these tumors has been increasing. They consist of a neuroendocrine neoplastic component with another component of adenocarcinoma usually and have a dismal prognosis. The rare GI pure neuroendocrine carcinoma is highly aggressive and requires complex and extensive management since a genetic distinction exists between it and GI non-neuroendocrine neoplasms, which are generally slow-growing lesions. The most common GI-mixed neuroendocrine non-neuroendocrine neoplasms are colorectal, followed by gastric, mainly in the gastroesophageal junction. Current imaging modalities of nuclear medicine and radiology play important roles in the accuracy of diagnosis. Liquid biopsy may contribute to early detection and timely diagnosis. Ultrasonography, either endoscopic or abdominal, is a technique that contributes to a diagnosis; additionally, contrast-enhanced ultrasonography is very helpful in follow-up appointments. Histopathology establishes a definite diagnosis and stage by evaluating the cell differentiation grade and the cell proliferation index Ki67. The genetic profile can be valuable in diagnosis and gene therapy. Surgical resection with wide lymphadenectomy, whenever possible, and adjuvant chemotherapy constitute the main therapeutic management strategies. Targeted therapy and immunotherapy achieve encouraging results.

Gastroenteropancreatic neuroendocrine carcinomas (GEP-NECs) constitute a rare and aggressive group of malignancies usually with widespread disease. There are limited studies on GEP-NECs, and therefore, we aim to acquire more information on the clinical features, treatment regimens, and prognosis.

Data from advanced GEP-NECs patients who had not previously received systemic treatment for advanced disease at The First Affiliated Hospital of Nanjing Medical University from 2010 to 2022 were retrospectively collected. Relationships between clinical-pathological features, treatment regimens, and prognosis were investigated using Kaplan-Meier curves and cox regression models.

A total of fifty-four patients were enrolled in the study. The median age was 65.5 years and 79.6% were male. At diagnosis, 51.9% and 3.7% of patients developed liver and brain metastasis respectively. Sixteen (29.6%) patients received chemotherapy according to primary site of tumor (PST), while thirty-eight (70.4%) were treated with etoposide-platinum (EP) regimen, which based on the first-line treatment of advanced small cell lung cancer (SCLC). No significant differences on progression-free survival (PFS) and response rate were observed between these two groups. Univariate survival analysis showed that liver metastasis, elevated baseline serum carcinoembryonic antigen, elevated baseline serum neuron-specific enolase, elevated baseline serum lactate dehydrogenase, and elevated baseline serum neutrophil-to-lymphocyte ratio (NLR) were associated with shorter PFS. After multivariate analysis, elevated NLR was the only factor that remained significantly associated with shorter PFS (P=0.01).

GEP-NECs are aggressive neoplasms, of which elevated NLR is proven to be an independent negative predictor. Treatment regimens based on PST are not inferior to regiments based on SCLC (EP) for GEP-NECs patients. Large-scale, prospective randomized controlled trials are required to establish the standard of care.

Gastroenteropancreatic neuroendocrine neoplasia (GEP-NEN) is a heterogeneous and complex group of tumors that are often difficult to classify due to their heterogeneity and varying locations. As standard radiological methods, ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography-computed tomography (PET/CT) are available for both localization and staging of NEN. Nuclear medical imaging methods with somatostatin analogs are of great importance since radioactively labeled receptor ligands make tumors visible with high sensitivity. CT and MRI have high detection rates for GEP-NEN and have been further improved by developments such as diffusion-weighted imaging. However, nuclear medical imaging methods are superior in detection, especially in gastrointestinal NEN. It is important for radiologists to be familiar with NEN, as it can occur ubiquitously in the abdomen and should be identified as such. Since GEP-NEN is predominantly hypervascularized, a biphasic examination technique is mandatory for contrast-enhanced cross-sectional imaging. PET/CT with somatostatin analogs should be used as the subsequent method.