# Pancreatic Neuroendocrine Tumors: From Benchside to Surgical Treatment

## TL;DR

This paper reviews the diagnosis and treatment of pancreatic neuroendocrine tumors, emphasizing new therapies and surgical approaches to improve patient outcomes.

## Contribution

The paper provides an updated overview of pNET management, highlighting new classification systems and emerging treatment strategies.

## Key findings

- The 2022 WHO classification distinguishes prognostic groups based on tumor differentiation and Ki-67 indices.
- Minimally invasive surgical techniques reduce morbidity while maintaining curative potential for localized pNETs.
- Systemic therapies like PRRT and mTOR inhibitors improve survival in advanced cases, though immunotherapy remains limited.

## Abstract

Pancreatic neuroendocrine tumors (pNETs) are rare, clinically heterogeneous neoplasms with rising incidence linked to improved diagnostics. This review examines pNET management, addressing epidemiology, classification, diagnosis, treatment, and emerging therapies. Epidemiologically, pNETs show higher prevalence in Western populations, with emerging associations to metabolic disorders. The 2022 WHO classification highlights distinct prognoses for well-differentiated NETs versus poorly differentiated NECs, guided by Ki-67 and mitotic indices. Non-functional tumors often present late, while functional variants manifest hormonal syndromes, necessitating tailored approaches. Advanced imaging (contrast-enhanced CT/MRI, 68Ga-DOTATATE PET) and endoscopic ultrasound-guided biopsy enable precise localization and grading. Surgical resection remains curative for localized disease, with minimally invasive techniques reducing morbidity. Active surveillance is favored for small (<2 cm), low-grade, non-functional tumors, while larger or aggressive lesions require resection. Systemic therapies, including mTOR inhibitors (everolimus), anti-angiogenics (surufatinib), and peptide receptor radionuclide therapy (PRRT), extend survival in advanced cases, though immunotherapy efficacy remains limited. Future strategies emphasize molecular profiling, biomarker development, and multidisciplinary integration to optimize outcomes. This evolving paradigm prioritizes precision medicine, balancing oncologic control with quality of life and functional preservation.