Endoscopic ultrasound-guided radiofrequency ablation of pancreatic insulinoma: a state of the art review

ABSTRACT

Introduction

Insulinomas are the most common functional pancreatic neuroendocrine tumors (PNETs) that lead to incapacitating hypoglycemia. Guidelines recommend surgical resection as the mainstay of management. However, surgery is fraught with complications, causing significant peri/post-operative morbidity. Since insulinomas are usually benign, solitary, small (<2 cm), and do not need lymphadenectomy, hence, in this regard, endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) is now being increasingly performed, to circumvent these adverse events and impairment of pancreatic function.

Areas covered

A comprehensive literature search was undertaken across various databases (PubMed/MEDLINE, Embase, Scopus), with no language restriction, for relevant articles (case series, reviews, case reports) pertaining to EUS-RFA for insulinoma and PNETs, till October 2023. In this review, we have explicated the role of EUS-RFA for insulinoma management, detailing thoroughly its mechanism of action, EUS-RFA devices with data on its safety and efficacy, and an algorithmic approach for its management.

Expert opinion

EUS-RFA is being advocated as a ‘mini-invasive’ option with the potential to replace surgery as a first-line approach for benign, sporadic, solitary, and small (<2 cm) insulinomas. Under real-time guidance, EUS-RFA has immense precision, is safe, predictable, with acceptable safety profile. Presently, it is being frequently performed for high-risk or inoperable candidates. Current need-of-the-hour is a randomized controlled trial to substantiate its role in the therapeutic algorithm for insulinoma management.

KEYWORDS:

• Insulinoma
• pancreas
• endoscopic ultrasound
• ablation
• radiofrequency ablation
• surgery
• adverse events

Article highlights

• Pancreatic insulinomas are functional pancreatic neuroendocrine tumors which leads to a clinical hyper-hormonal syndrome (endogenous hyperinsulinemia) causing hypoglycemia, which dictates its diagnosis, due to neuroglycopenic and autonomic signs and symptoms.

• Since decades, surgical resections have been the cornerstone in its treatment algorithm, since all insulinomas, irrespective of their size, have to be treated. Surgical resection, whether open or laparoscopic, ranging from enucleation to morbid pancreaticoduodenectomy, is replete with significant complications, most commonly post-operative pancreatic fistula, leading to considerable peri-/post-operative morbidity with impairment of pancreatic function (exocrine/endocrine).

• In the current scenario, this peculiar disease needs a personalized approach toward its management, ranging from localization, histological diagnosis followed by defining the best curative treatment, that is minimally invasive with least post-intervention consequences (adverse events, quality of life, pancreatic function). In this regard, endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) has glaringly come into the spotlight, as an alternative option to surgical management of insulinoma.

• Under real-time endosonographic guidance, EUS-RFA has amassed enough scientific evidence recently, that allows selective tumor ablation, with extensive precision, and minimal damage to surrounding parenchyma. Awareness about use of EUS-RFA is exemplified by the fact that its being routinely performed worldwide for high-risk as well as inoperable candidates.

• It is important to note that while using EUS-RFA, it’s the ‘slow, methodical energy deposition’ that generates the best results, as compared to sudden temperature rise, for the purpose of intentional tissue ablation. This phenomenon, named ‘thermal diffusivity effect’ causes greater but slower diffusion of thermal damage within the neoplastic mass, but not outside, making it a safe procedure.

• The EUSRA (STARmed) EUS-RFA probe is the only commercially available probe in the market that comes with its generator. Multiple studies have been published on its use for insulinoma management, with a recent multicenter study highlighting lower adverse events with EUS-RFA, compared to surgical resections.

• An ideal candidate for EUS-RFA in a pancreatic insulinoma, is a tumor that is benign (grade 1 or 2), solitary, small <2 cm size, no association with genetic syndromes and ≥1 mm distance from main pancreatic duct.

• An urgent necessity at the moment is a randomized trial, comparing EUS-RFA with surgery (gold standard) which will firmly establish the role of EUS-RFA in the therapeutic algorithm for pancreatic insulinoma management, as well as a step-up approach in case of clinical failure.

Abbreviations

EUS	=	endoscopic ultrasound
RFA	=	radiofrequency ablation
CT	=	computed tomography
MRI	=	magnetic resonance imaging
PET	=	positron emission tomography
FNB	=	fine needle biopsy
MEN	=	multiple endocrine neoplasia
LN	=	lymph node
PAC	=	pre-anesthetic checkup
MPD	=	main pancreatic duct
F/U	=	follow up
CE-EUS	=	contrast enhanced endoscopic ultrasound

Note: Definitions (as proposed by Crinò et al. [96]):

*Complete response: complete disappearance of symptoms related to the hyper-hormonalsecretion syndrome

#Symptoms persistence: irresolution of symptoms or their appearance within 6 months aftertreatment

#Symptoms recurrence: Relapse of symptoms after a period of wellness of at least 6 months.

$Treatment failure: After 2 EUS-RFA sessions, patients with symptoms persistence (even ifmitigated), or requirement of medical therapy, or lesion recurrence(metachronous lesion(s) will need to be excluded). Lesion recurrencewill be defined as the rate of patients with the appearance onimaging of local solid mass, or lymph nodes, or distant metastasessuspicious for disease recurrence.

Declaration of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/17474124.2024.2321938

Additional information

Funding

This paper was not funded.