Endoscopic ultrasound-guided ablation of pancreatic neuroendocrine tumors: with or without alcohol?

I read with great interest the E-Video publication by Silva et al., “Endoscopic ultrasound-guided fine needle injection of alcohol for ablation of an insulinoma: a well-documented successful procedure,” published in the March issue of Endoscopy [1]. The authors describe a successful endoscopic ultrasound (EUS)-guided alcohol ablation of a functional pancreatic neuroendocrine tumor (pNET) with excellent results. No adverse events occurred and glucose levels returned to normal only 2 weeks post treatment. It was therefore stated that this technique is safe and efficacious. Although we certainly share the authors’ enthusiasm about this particular case, several important remarks have to be made regarding this statement.

The therapeutic use of alcohol in biliopancreatic disorders has been associated with various adverse events, such as pancreatitis and secondary sclerosing cholangitis, both of which are caused by local caustic effects. In EUS-guided alcohol ablation specifically, significant rates of treatment-related pancreatitis have been reported, varying from 6 % to 12.5 % [2, 3]. A randomized controlled trial in 2017 compared an alcohol-free protocol with an alcohol-containing ablation protocol in EUS-guided chemotherapeutic ablation of pancreatic mucinous neoplasms. This study revealed that omitting alcohol from the ablation protocol, resulted in a significant reduction in adverse events, as all episodes of pancreatitis occurred in the alcohol-containing protocol (in 6 % of patients vs. none in the alcohol-free protocol) [3]. Although one could argue that this may have negative effects on efficacy, the same trial showed that omitting alcohol from the ablation protocol did not lead to reduced complete ablation rates when used in the context of chemotherapeutic ablation. In regard to safety, it therefore seems that patients would benefit from an alcohol-free technique.

Efficacy is another important problem concerning alcohol ablation of pancreatic lesions. In 2016, the largest follow-up of pNETs treated with EUS-guided alcohol ablation was published. This study, containing 11 pNETs as well as 33 serous cystic neoplasms and 9 intraductal pancreatic mucinous neoplasms (IPMNs), showed that only little over half of patients with pNETs had a radiological response [4]. Despite multiple sessions in three patients, efficacy rose only discretely from 53.8 % to 61.5 %. Although efficacy was significantly higher amongst patients with pNETs compared to IPMNs (11 %, P < 0.001), a more efficient technique is desperately needed. EUS-guided radiofrequency ablation (RFA) might provide such effectiveness, as only very recently promising results of a prospective multicenter study were published, with 86 % of treated pNETs showing resolution after 1 year of follow-up [5].

In conclusion, EUS-guided ablation of pNETs provides an important alternative to surgery. However, the suboptimal safety profile, together with relatively low complete ablation rates for alcohol-containing protocols, suggest that alternative ablation techniques, such as EUS-guided RFA, should be considered.

• References

• 1 Silva FAOB, Colaiacovo R, Araki O. et al. Endoscopic ultrasound-guided fine needle injection of alcohol for ablation of an insulinoma: a well-documented successful procedure. Endoscopy 2019; 51: E57-E58
• 2 Paik WH, Seo DW, Dhir V. et al. Safety and efficacy of EUS-guided ethanol ablation for treating small solid pancreatic neoplasm. Medicine (Baltimore) 2016; 95: e2538
• 3 Moyer MT, Sharzehi S, Mathew A. et al. The safety and efficacy of an alcohol-free pancreatic cyst ablation protocol. Gastroenterology 2017; 153: 1295-1303
• 4 Park JK, Song BJ, Ryu JK. et al. Clinical outcomes of endoscopic ultrasonography-guided pancreatic cyst ablation. Pancreas 2016; 45: 889-894
• 5 Barthet M, Giovannini M, Lesavre N. et al. Endoscopic ultrasound-guided radiofrequency ablation for pancreatic neuroendocrine tumors and pancreatic cystic neoplasms: a prospective multicenter study. Endoscopy 2019; [Epub ahead of print]