Pancreatic neuroendocrine tumors - going beyond surgery. Literature review and experience of a tertiary center

Abstract

Background: Surgery is the standard therapy for pancreatic neuroendocrine tumors (pNETs), but since post-resection fistulae and other surgery related complications are common, new minimal invasive approaches are emerging. Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) is a promising tool for pNETs, with a good safety profile and favorable results.

Patients, materials and methods: This is a single-center, retrospective case series including all patients with functional (F) and non-functional (NF) pNETs treated with EUS-RFA in the Department of Gastroenterology, Emergency Clinical Hospital of Bucharest, Romania, between March 2023 and March 2024 and followed for a mean period of 11.6 months. Technical success, clinical, sonographic and radiological response, adverse events (AEs) rate and severity were assessed.

Case series: A total of five out of nine EUS-RFA were performed for pNETs, with a majority of NF-pNETs. In this pNET group, the mean size of the lesions was 13 mm. Technical success was achieved in 100% of patients and persistent clinical remission of hypoglycemia in the insulinoma case was attained. In the NF-pNET subgroup, two patients were successfully radiologically treated with complete disappearance of the lesions, one lesion showed cystic transformation, and one had modest size reduction at follow-up imagery. One procedure-related early AE occurred: mild abdominal pain with quick resolution. No major complications, nor death were reported.

Conclusions: Reports from this literature review and small case series suggest that EUS-RFA can be effective in both F- and NF-pNETs, offering the best combination of real-time imaging guidance and minimal invasiveness with no severe AEs and short hospital stay.

Keywords: EUS-RFA; NF-pNETs; insulinoma; neuroendocrine tumors; pancreas.

Figure 1

EUS image of a hypoechogenic lesion (insulinoma before EUS-FNB). EUS: Endoscopic ultrasound; FNB: Fine-needle biopsy

Figure 2

(A) CT in arterial phase showing a body tail-enhanced lesion; (B) Proliferation of small to medium monotonous cells with coarse nuclear chromatin and minimal atypia, pink cytoplasm – the tumoral cells are arranged in solid nests (HE staining, ×400); (C) Chromogranin A IHC staining (×400) reveals positive tumoral cells (brown colored) in contrast to acinar pancreatic tissue; (D) IHC staining for Ki67 (×100) reveals rare positive nuclei (brown colored), a Ki67 index less than 2%; (E) EUS evaluation of a pancreatic body hypoechogenic lesion; (F) EUS-RFA ablation in a patient with NF-pNET. Histopathology and immunohistochemistry microscopy images: Leica DM750 microscope; LEICA IC50W camera for image capture; Leica Application Suite image acquisition and processing system. CT: Computed tomography; EUS: Endoscopic ultrasound; HE: Hematoxylin–Eosin; IHC: Immunohistochemical; NF: Non-functional; pNET: Pancreatic neuroendocrine tumor; RFA: Radiofrequency ablation

Figure 3

– (A) Before procedure T1-weighted MRI imaging showing pancreatic head lesion; (B) Post EUS-RFA T1-weighted MRI imaging showing pancreatic lesion decreasing in size. EUS: Endoscopic ultrasound; MRI: Magnetic resonance imaging; RFA: Radiofrequency ablation

Figure 4

(A) Pancreatic tissue biopsy fragment with fibrotic area in which are observed small cellular aggregates with variable shape – no mitotic activity, no necrosis (HE staining, ×100); (B) Chromogranin A IHC staining (×100) reveals positive tumoral cellular aggregates (brown colored) in contrast to acinar pancreatic and fibrotic tissues; (C) EUS images of a pancreatic head hypoechogenic lesion; (D) EUS-RFA procedure of the lesion; (E) Abdominal CT scan before EUS-RFA; (F) Abdominal CT scan after EUS-RFA – absence of head pancreatic lesion. Histopathology and immunohistochemistry microscopy images: Leica DM750 microscope; LEICA IC50W camera for image capture; Leica Application Suite image acquisition and processing system. CT: Computed tomography; EUS: Endoscopic ultrasound; HE: Hematoxylin–Eosin; IHC: Immunohistochemical; RFA: Radiofrequency ablation

Figure 5

(A) CT in arterial phase showing a round, well-defined, moderately enhanced pancreatic isthmo-corporeal lesion with iodine concentrations similar to that of the spleen; (B and C) Four months follow-up MRI after EUS-RFA ablation showing findings consistent with cystic changes secondary to treatment – hypointense on T1-weighted imaging (B) and hyperintense on T2-weighted imaging (C). CT: Computed tomography; EUS: Endoscopic ultrasound; MRI: Magnetic resonance imaging; RFA: Radiofrequency ablation