Endoscopic ultrasound-guided ablation of small pancreatic neuroendocrine neoplasms: Bridging the gap between surveillance and surgery

Table 4 Main clinical studies of endoscopic ultrasound-guided ablation in pancreatic neuroendocrine neoplasms

Ref.	Design	Population	Technique	Main efficacy and safety outcomes	Follow-up	Main limitations
Park et al[70], 2015	Retrospective, single center	11 patients; 14 panNENs < 20 mm; 10 NF-panNENs, 4 insulinomas; 2 MEN1; mean size 12.3 mm	EUS-EA; 18 sessions	Technical success 100%; complete radiological response 53.8% after one session and 61.5% after retreatment; symptom resolution in 2/2 insulinomas; pancreatitis in 3 patients and 1 duct stricture	Median 370 days	Small uncontrolled cohort; mixed tumors; variable ethanol dose and sessions; imaging-based response; short follow-up
Choi et al[71], 2018	Prospective, single center	33 patients; 40 panNENs < 20 mm; 39 NF-panNENs, 1 insulinoma; median size 11 mm; 3 hereditary cases	EUS ethanol-lipiodol ablation; 63 sessions	Technical success 100%; complete ablation 60%; pancreatitis in 2/63 sessions; radiological-pathological concordance 86% in 22 reassessed tumors	Median 42 months	No control group; single expert operator; repeat FNB available in only 22/40 tumors; 3 radiological complete responses reclassified as incomplete
Barthet et al[84], 2021	Prospective, multicenter, non-randomized	12 patients; 14 G1 NF-panNENs < 20 mm; mean size 13.1 mm; 1 MEN1	EUS-RFA	Complete disappearance/necrosis 85.7% at 1 year and final follow-up; 1 late recurrence, 1 delayed response, and 1 persistent failure followed by liver metastases after initial undergrading	Mean 45.6 months	Very small panNEN subgroup; mixed study cohort; no control group; protocol evolved during the study; response mainly imaging based
Marx et al[35], 2022	Retrospective, two centers	27 patients with sporadic G1 NF-panNENs; mean size 14.0 mm, range 7-25	EUS-RFA	Technical success 100%; complete radiological response 85.2% after one session and 92.6% overall; pancreatitis 14.8%; 3 grade IIIb complications; surgical specimen in 1 patient showed 3-mm residual tumor	Mean 15.7 months	Small selected cohort; no comparator; short and heterogeneous follow-up; imaging-based response; clinically relevant AE rate
Napoléon et al[75], 2023	National, multicenter, retrospective	100 patients; 104 pancreatic neoplasms, including 64 panNENs and 16 functioning tumors; median overall size 15 mm	EUS-RFA; 116 sessions	Technical success 97%; overall complete response 60.2%; panNEN histology and size < 20 mm predicted complete response; 22 AEs; MPD distance ≤ 1 mm independently predicted AEs	Imaging planned at 1 month, 6 months, and 12 months	Heterogeneous tumor types; panNEN-specific outcomes incompletely separated; variable protocols across 20 centers; non-standardized longer-term follow-up
Yan et al[99], 2023	Prospective, single center	9 high-risk or surgery-refusing patients with symptomatic insulinomas; 5 previously operated; 1 multifocal case	EUS-EA; 14 procedures	Initial clinical response 77.8%; relapse in 55.6%; 4 patients remained relapse-free long term; repeat-ablation response 40%; pancreatitis in 1/14 procedures	Median 994 days	Very small cohort; no control group; highly selected patients; heterogeneous tumor burden; clinical rather than oncological endpoint
Crinò et al[36], 2023	International, multicenter, retrospective propensity-matched study	178 patients with sporadic insulinomas: 89 EUS-RFA and 89 surgery; mean size 13.5 mm	EUS-RFA vs surgery	AEs 18.0% vs 61.8%; severe AEs 0% vs 15.7%; clinical efficacy 95.5% vs 100%; shorter hospital stay after RFA; recurrence after RFA 16.9%	Median 23 vs 37 months	Non-randomized design; residual confounding possible; shorter follow-up after RFA; clinical rather than histological efficacy endpoint
Matsumoto et al[72], 2025	Prospective, multicenter, single arm with historical surgical comparison	25 patients with G1 NF-panNENs ≤ 15 mm; median size 10.1 mm; MPD distance ≤ 2 mm excluded	Standardized EUS-EA with early reassessment and retreatment	Complete ablation 88% at 1 month and 6 months; 32% required early retreatment; severe AEs 4%; pancreatitis 20%; new or worsening diabetes 12%; no conversion to surgery	6 months	Small single-arm cohort; historical control; very short follow-up; imaging-based endpoint; highly selected tumors
Okasha et al[100], 2025	Prospective, multicenter cohort	27 patients: RFA group included 11 insulinomas and 2 PDACs; EA group included 13 insulinomas and 1 NF-panNEN	EUS-RFA or EUS-EA	RFA: Complete insulinoma response 10/11 and partial response 1/11, with no reported AEs. EA: Complete response 8/14, partial response 2/14, failure 4/14; pancreatitis in 4/14	Mean 12.0 months for RFA and 9.6 months for EA	Small heterogeneous cohort; non-comparative groups; unclear grading; clinical endpoints; short follow-up; internal reporting inconsistencies

AEs: Adverse events; EA: Ethanol ablation; EUS: Endoscopic ultrasound; MEN1: Multiple endocrine neoplasia type 1; MPD: Main pancreatic duct; NF-panNENs: Non-functioning pancreatic neuroendocrine neoplasms; panNENs: Pancreatic neuroendocrine neoplasms; PDACs: Pancreatic ductal adenocarcinomas; RFA: Radiofrequency ablation; EUS-RFA: Endoscopic ultrasound-guided radiofrequency ablation; EUS-EA: Endoscopic ultrasound-guided ethanol ablation; FNB: Fine-needle biopsy.