Surgical Management of Neuroendocrine Tumours of the Pancreas

Abstract

Neuroendocrine tumours of the pancreas (pNET) are rare, accounting for 1–2% of all pancreatic neoplasms. They develop from pancreatic islet cells and cover a wide range of heterogeneous neoplasms. While most pNETs are sporadic, some are associated with genetic syndromes. Furthermore, some pNETs are ‘functioning’ when there is clinical hypersecretion of metabolically active peptides, whereas others are ‘non-functioning’. pNET can be diagnosed at a localised stage or a more advanced stage, including regional or distant metastasis (in 50% of cases) mainly located in the liver. While surgical resection is the cornerstone of the curative treatment of those patients, pNET management requires a multidisciplinary discussion between the oncologist, radiologist, pathologist, and surgeon. However, the scarcity of pNET patients constrains centralised management in high-volume centres to provide the best patient-tailored approach. Nonetheless, no treatment should be initiated without precise diagnosis and staging. In this review, the steps from the essential comprehensive preoperative evaluation of the best surgical approach (open versus laparoscopic, standard versus sparing parenchymal pancreatectomy, lymphadenectomy) according to pNET staging are analysed. Strategies to enhance the short- and long-term benefit/risk ratio in these particular patients are discussed.

Oncolytic vaccinia virus injected intravenously sensitizes pancreatic neuroendocrine tumors and metastases to immune checkpoint blockade

“…administration of a vaccinia virus combined with aPD1 has abscopal growth-slowing activity on a second implanted tumor, 10 , 12 still unknown until the current study was whether a vaccinia virus plus aPD1 promoted regression of existing liver metastases that develop from spontaneous tumors and recapitulate aggressive human PanNETs. 5 , 55 , 56 …”

“…administration of a vaccinia virus combined with aPD1 has abscopal growth-slowing activity on a second implanted tumor, 10,12 still unknown until the current study was whether a vaccinia virus plus aPD1 promoted regression of existing liver metastases that develop from spontaneous tumors and recapitulate aggressive human PanNETs. 5,55,56 To address these issues, we evaluated anti-metastatic activity in the context of tumor targeting and changes in tumor cells and immune cells in PanNET metastases in RT2;AB6F1 mice. Importantly, metastases, like primary tumors, were infected after i.v.…”

Gastroenteropancreatic neuroendocrine neoplasms: A clinical snapshot

“…The North American Neuroendocrine Tumor Society consensus paper on the surgical management of pancreatic neuroendocrine tumors (2020) has suggested the following surgical options[ 82 ]. Surgery is indicated for non-functional pNENs that are symptomatic or ≥ 2 cm in size and for all functional pNENs regardless of their size, except MEN1 associated gastrinomas that are small (< 2 cm).…”

Prognostic value of DAXX/ATRX loss of expression and ALT activation in PanNETs: is it time for clinical implementation?

“…On the contrary, localised well-differentiated PanNETs, especially those <2 cm, have a more indolent behaviour with 5 years survival of 93% of patients. 1 Death domain-associated protein ( DAXX ) and or alpha-thalassemia/mental retardation X-linked chromatin remodeler ( ATRX ) are mutated in almost 40% of sporadic PanNETs, often in combination with MEN1 mutations. 2 DAXX/ATRX mutations result in loss of nuclear expression of the protein in the tumour tissue.…”