Surgical management of pancreatic neuroendocrine liver metastases

Abstract

Pancreatic neuroendocrine tumors (PNET) are a heterogeneous group of neoplasms that vary in their clinical presentation, behavior and prognosis. The most common site of metastasis is the liver. Surgical resection of neuroendocrine liver metastases (NELM) is thought to afford the best long-term outcomes when feasible. Initial preoperative workup should include surveillance for carcinoid syndrome, screening for evidence of liver insufficiency, and performance of imaging specific to neuroendocrine tumors such as a somatostatin receptor positron emission tomography scan. Standard surgical principles apply to hepatic surgery for NELM, namely prioritizing low central venous pressure anesthesia, minimizing blood loss, knowledge of liver anatomy, generous use of intraoperative ultrasound, as well as safe parenchymal transection techniques and practices to avoid bile leakage. Knowledge of established prognostic factors may assist with patient selection, which is important for optimizing short-and long-term outcomes of hepatic resection. Adjunct therapies such as concomitant liver ablation are used frequently and are generally safe when used appropriately. For patients with synchronous resectable NELM, resection of the primary either in a staged or combined fashion is recommended. Primary tumor resection in the setting of unresectable metastatic disease is more controversial, however generally recommended if morbidity is acceptable. For patients who are not surgical candidates, due to either patient performance status or burden of liver disease, several liver-directed therapies such as transarterial embolization, chemoembolization, and radioembolization are available to assist with locoregional control, extend progression-free survival (PFS), and improve symptoms of carcinoid syndrome. Multiple systemic therapy options exist for patients with metastatic PNET which are often prioritized for those patients with advanced or progressive disease. A systematic approach in a multi-disciplinary setting is likely to result in the best long-term outcomes for patients with pancreatic NELM. Ongoing research is needed to determine the optimal patient selection for hepatic surgery as well as the ideal treatment sequencing for those patients with NELM.

Current and New Challenges in the Management of Pancreatic Neuroendocrine Tumors: The Role of miRNA-Based Approaches as New Reliable Biomarkers

“…Primary tumor resection can be considered for selected patients with unresectable liver metastases, as it has been associated with improved survival [35]. Local ablative therapies can also be used in patients with unresectable metastatic disease, alone or in combination with liver resection [36].…”

Surgical Indications and Outcomes of Resection for Pancreatic Neuroendocrine Tumors with Vascular Involvement

“…The use of positron emission tomography (PET), using somatostatin analogues labeled with positron-emitting gallium 68 dota peptides ( 68 Ga-DOTATATE), has been shown to be very accurate for detecting many types of NETs [33]. Specifically for pNETs, 68 Ga-DOTATATE is beneficial in the overall clinical management of patients, its identification of unknown primary tumors, metastases to the liver, and assessment of global tumor burden in extrahepatic disease [34]. However, it does not provide the anatomical detail required for surgical planning of vascular involvement and is not performed routinely for locally advanced pNETs without distant disease.…”

Pancreatic neuroendocrine neoplasms — update of the diagnostic and therapeutic guidelines (recommended by the Polish Network of Neuroendocrine Tumours) [Nowotwory neuroendokrynne trzustki — uaktualnione zasady diagnostyki i leczenia (rekomendowane przez Polską Sieć Guzów Neuroendokrynych)]

“…Cytoreductive surgery can be performed with resection and/or ablation of liver lesions [116]. RFA is applicable when there are less than 10 focal lesions in the liver, and the largest of them is less than 5 cm in diameter (optimally 3 cm).…”

“…Cytoreduction of liver lesions is considered advisable when the tumour mass can be reduced by min. 70% (especially in patients with F-PanNET or carcinoid syndrome) [2,[116][117][118].…”

“…Radical excision of liver metastases is the gold standard in the treatment of advanced PanNET, so whenever resection is possible, it should be performed [116]. The method of resection depends on the patient's general condition, size, location, and number of lesions, and includes enucleation, hepatic wedge resection, segmental resection, non-anatomical resection, or hemihepatectomy.…”