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Pancreatic neuroendocrine tumors (PNETs) are rare, making up less than 2% of all pancreatic cancers with an incidence of 0.48 per 100,000 persons [1-3]. PNETs are a group of tumors that develop due to uncontrolled proliferation of neuroendocrine cells in the pancreas and can be classified as either functioning or non-functioning. Functioning PNETs are named after the hormone they make, and cause symptoms related to hormone hypersecretion [4]. Examples of functioning PNETs include insulinoma, glucagonoma, gastrinoma, and VIPoma among others [4]. Non-functioning PNETs do not make enough hormones to cause symptoms which can allow them to grow large and metastasize undetected over time [3,4]. Compared to the more common pancreatic adenocarcinoma, which has a median survival time of 6-months, PNET prognosis is more favorable with a 4.1- year median survival time [5]. Patients with stage 1 PNETs have 5-year survival rates ranging from 90-100% whereas those with stage 4 disease have a 60% 5-year survival rate [6]. In cases of local, low-grade neoplasms, parenchymal sparing surgery including enucleation is sometimes considered [7]. For metastatic PNETs, the current surgical standard of care is pancreaticoduodenectomy [8].

As a less invasive alternative to radical surgery, ablative techniques have been rising in popularity over the last several years for treatment of pancreatic cancers. Thermal ablative therapies including Radio frequency Ablation (RFA) and Microwave Ablation (MWA) first became widespread for their use in local tumor ablation in the early 2000’s. These technologies rely on extreme hyperthermia to destroy tissue. While tissue destruction is effective, there is a risk of damaging surrounding vessels and structures with the high intensity heat generated [9,10]. In 2011, NanoKnife, a new type of non-thermal ablation device using Irreversible Electroporation (IRE), was approved by the FDA. IRE destroys tumors by generating electrical fields between probes placed around target soft tissue and delivering pulses that create permanent nanopores in cell membranes, thereby disrupting homeostasis [11]. Irreversible cellular swelling through the pores leads to apoptosis and cell death [11]. One major advantage of IRE is its ability to preserve critical surrounding structures in highly vascular areas [9]. Previously, IRE has been shown to be an effective ablation therapy for locally advanced pancreatic adenocarcinoma (LAPC) tumors [12]. Up to this point, IRE efficacy for treatment of PNETs has not been clearly determined. Though metastatic disease is frequently treated with ablative techniques (typically liver), the scenario is switched in this case by resecting the metastases but treating the primary with ablation. This is the first report of our knowledge of IRE as an alternative treatment in the setting of a metastatic PNET.

Case Presentation

This is a 50-year-old Caucasian male with no significant past medical history who presented to his primary care doctor in January 2021 with complaints of diarrhea and dyspepsia for two months. Laboratory results revealed transaminasemia and elevated alkaline phosphatase. Esophagogastroduodenoscopy showed ulcers in the gastroesophageal junction and the second and third part of the duodenum. Patient was started on omeprazole, famotidine, and sucralfate which improved his symptoms. Further laboratory workup showed an elevated gastrin level of 743 pg/mL and chromogranin A of 1874 ng/mL.

He underwent abdominal Computed Tomography (CT) in June 2021 which showed a 6.5 cm hypervascular lesion in the right liver lobe along with pancreatic ductal dilation. Biopsy of the liver lesion revealed a well-differentiated grade 2 neuroendocrine tumor with a Ki-67 of 4.9%. Gallium-68 dotatate PET/CT scan redemonstrated the liver lesion along with a pancreatic head mass and peripancreatic lymph node enlargement (Figures 1, 2). Biopsy of the peripancreatic lymph nodes further demonstrated a well differentiated grade 2 neuroendocrine tumor.

## Figure 1:

Uptake lesion demonstrated in the pancreas on Positron Emission Tomography (PET) scan (July 2021).