Gastroenteropancreatic neuroendocrine neoplasms: current development, challenges, and clinical perspectives

Abstract

Neuroendocrine neoplasms (NENs) are highly heterogeneous and potentially malignant tumors arising from secretory cells of the neuroendocrine system. Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are the most common subtype of NENs. Historically, GEP-NENs have been regarded as infrequent and slow-growing malignancies; however, recent data have demonstrated that the worldwide prevalence and incidence of GEP-NENs have increased exponentially over the last three decades. In addition, an increasing number of studies have proven that GEP-NENs result in a limited life expectancy. These findings suggested that the natural biology of GEP-NENs is more aggressive than commonly assumed. Therefore, there is an urgent need for advanced researches focusing on the diagnosis and management of patients with GEP-NENs. In this review, we have summarized the limitations and recent advancements in our comprehension of the epidemiology, clinical presentations, pathology, molecular biology, diagnosis, and treatment of GEP-NETs to identify factors contributing to delays in diagnosis and timely treatment of these patients.

Keywords: Chemotherapy; Diagnosis; Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs); Immunotherapy; Neuroendocrine neoplasms (NENs).

Fig. 1

The diagnosis and management of GI-NENs. In different locations of the gastrointestinal tract, including the stomach, colon, and rectum, among others, tumors have been observed. Different strategies can be utilized to diagnose these tumors, including biochemical characteristics, MRI, biopsy, and endoscopy. According to the size of the tumor and grade, surgical resection can be recommended. Hence, the management of these tumors differs based on their origin, tumor size, and tumor grade. EUS endoscopic ultrasound, US ultrasound, CT computed tomography, MRI magnetic resonance imaging, SSTR-PET/CT somatostatin receptor-positron emission tomography/computed tomography, NE neuroendocrine, FUP follow-up, PPI proton pump inhibitor, LAR long-acting release, PRRT peptide receptor radionuclide therapy, T tumor, NETs neuroendocrine tumors, GI-NENs gastrointestinal neuroendocrine neoplasms

Fig. 2

The diagnosis and management of pNENs. The management of functional and non-functional pNENs differs. However, similar examinations, including MRI, chest CT, and biopsy, can be performed for the diagnosis of these tumors. Disease management depends on the disease type, tumor size, and functional or non-functional status. EUS endoscopic ultrasound, US ultrasound, CT computed tomography, MRI magnetic resonance imaging, SSTR-PET/CT somatostatin receptor-positron emission tomography/computed tomography, PPI proton pump inhibitor, LAR long-acting release, pNEN pancreatic neuroendocrine neoplasm, SSAs somatostatin analogs, RT radiotherapy, PRRT peptide receptor radionuclide therapy, CAPTEM capecitabine and temozolomide, VIP vasoactive intestinal polypeptide