Surgical management of small intestinal neuroendocrine tumours

Gastroenteropancreatic neuroendocrine neoplasms (NENs) originate from neuroendocrine cells across the body; they are increasing in incidence and prevalence, as documented across several regions1–3. The most frequent sites of NENs include the small intestine and the pancreas. The prevalence of small intestinal NENs was most recently estimated at 45 per 100 000 people and that of pancreas NENs at 35 per 100 000 people compared with 10 per 100 000 people for pancreatic adenocarcinoma for example3,4. As a result, most surgeons will encounter gastroenteropancreatic NENs in their practice. The management of gastroenteropancreatic NENs, including work-up, diagnosis, staging, and treatment, varies based on the specific site of the primary tumour. NENs include neuroendocrine tumours (NETs) and neuroendocrine carcinomas (NECs); NETs are well-differentiated malignancies while NECs are poorly differentiated and present with more aggressive behaviour5. This article will focus on NETs. Small intestinal neuroendocrine tumours (SI-NETs) have different biology compared with other epithelial cancers and, hence, have different considerations for management than most other gastrointestinal cancers. Three features of SI-NETs drive these considerations: prolonged survival, endocrine hypersecretion, and fibrosis within the tumour environment. Prolonged survival is often observed, even in patients with locally advanced or widely metastatic disease2,3. Both endocrine hypersecretion and fibrosis (desmoplastic reaction) can contribute to deteriorating quality of life over the course of disease via systemic endocrine syndrome and locoregional complications6–8. As such, oncological control must be pursued along with preservation of intestinal function and quality of life. To do so, multidisciplinary care involving several disciplines is critical to devise tailored management plans. Despite the prevalence of SI-NETs in surgical practice, the operative management of SI-NETs lacks standardization. Decision-making and recommendations are informed largely by retrospective, single-centre (often single-surgeon) series. Compared with systemic therapy for NETs, surgical evidence is sparse and heterogeneous. Indeed, the field overall has advanced rapidly, particularly in biomarker discovery, imaging, and systemic therapy, but surgical strategies have remained largely unchanged. This contrast underscores the opportunity for better evidence and innovation in the operative care of patients with SI-NETs. This article aims to provide insights into existing clinical dilemmas in the surgical care of patients with SI-NETs as well as current and future directions. Rather than attempt to provide an exhaustive review of SI-NETs, it focuses on key clinical challenges that commonly arise in practice and areas where evidence is evolving and likely to influence surgical management.