**5. Additional indications: margin accentuation IRE**

In recent years, the indications of IRE have been expanded to the so-called "margin accentuation" IRE, typically in patients with borderline resectable pancreatic cancer. In this patient group, IRE is used as an adjunct to surgery intraoperatively, aiming to achieve a higher percentage of negative margin resections [32]. It is well known that margin-negative resection is a strong indicator for better overall survival in pancreatic cancer. However, isolated local recurrences are observed in 35–80% of patients after intended R0 resection, raising the hypothesis that R1 resections are underestimated [54, 55]. A comprehensive work-up done by Esposito et al. confirmed that almost 80% of the patients had a true R1 resection, if a thorough examination is performed by the pathologist [56]. It is commonly accepted that R1 resections are associated with worse outcome as compared to R0 resections. In addition, there are different R0 definitions used in the current literature: no microscopic tumor at the or within 1 mm of the resection margin [57]. Hence, the role of R1 resections is not yet entirely clear—some advocate that R1 margins have a negative impact on the overall survival, whereas others state that R1 margins do influence local recurrence rates, without having a significant effect on survival [58–61]. Margin-accentuation IRE has been implemented in multiple pancreatic centers aiming to achieve a higher "true" R0 percentage and to therefore potentially increase overall survival and decrease local recurrences. At the present time, there are no clear recommendations of when margin accentuation IRE should be performed, because there are no clear radiological signs of when a microscopic positive resection margin has to be expected. Given the true R1-resection rate of up to 80%, one might argue that every patient with suspected or proven pancreatic cancer should have a margin accentuation IRE, if the additional procedure risk is limited and operation time is not significantly prolonged. However, as long as no data are published on the benefit of margin accentuation IRE over surgical resection only, the indication remains somewhat arbitrary. Further research is definitely needed to assess the independent effect of margin accentuation IRE on local recurrence rates and overall survival.
