The final ablation zone created with irreversible electroporation (IRE) depends on the size, shape and strength of the electric field that is influenced by several parameters. A profound understanding of the effect of IRE parameter alterations on the electric field are a prerequisite for a safe and effective treatment. Here, we demonstrate a semolina in castor oil model that enables visualization of the static electric field developed by a high-voltage generator between two needle-electrodes. We intuitively visualize the variation in electric field line pattern for selected IRE parameters; active needle length, inter-needle distance, applied voltage and presence of a nearby metal stent, by cameras in three dimensions. The observations were compared to and supported by two-dimensional numerical simulations of the electric field. Our semolina model visualizes the disturbance of the electric field by a metal stent, potentially leading to an incomplete tumour ablation between the needles. The reduction in electric field strength and the area at risk for incomplete tumour ablation are confirmed by the numerical simulations. The semolina model provides insight in the fundamental physics of the electric field, the effect of alterations in IRE parameter combinations and presence of a metal stent within the ablation zone. Irreversible electroporation (IRE) is theoretically a non-thermal ablation technique, which makes it especially suitable for ablation of tumours near vital structures, such as locally advanced pancreatic tumours 1-3. IRE uses a high-voltage external electric field and electric pulses of microsecond duration to change the transmembrane potential of tumour cells, resulting in permanent permeabilization of the cell membrane 4-6. Membrane permeabilization disturbs the cell's mechanisms to maintain homeostasis, finally leading to cell death via a necrotic pathway presumably or apoptosis 4,7-9. Tumour cells are ablated while the extracellular matrix, collagen and elastic fibres, such as blood vessels and bile ducts remain intact 9,10. Biliary drainage is frequently required in patients with pancreatic tumours. The use of a metal stent is usually preferred because of fewer stent-related complications (e.g. cholangitis) and less stent dislocations compared to plastic stents 11,12. It is currently unknown whether IRE can be safely and effectively applied in patients with a metal stent in situ close to the ablation site. Detrimental effects of a metal object on IRE outcomes have been suggested in literature. In a case report, severe complications have been described after IRE treatment in the proximity of a metal stent, potentially caused by unintended thermal effects 13. A retrospective clinical study demonstrated that IRE near small metal surgical clips (< 1 cm to tumour margin or needle electrodes) resulted in distortion of the electric field and inadequate coverage of the tumour, a less effective cell death and reduced treatment efficacy 14. The presence of a metal clip was also significantly related to local ...

Introduction: The aim of this study was to review the effect of irreversible electroporation parameter settings on the size of the ablation zone and the occurrence of thermal effects. This insight would help to optimize treatment protocols and effectively ablate a tumor while controlling the occurrence of thermal effects. Methods: Various individual studies report the influence of variation in electroporation parameters on the ablation zone size or occurrence of thermal effects. However, no connections have yet been established between these studies. With the aim of closing the gap in the understanding of and personalizing irreversible electroporation parameter settings, a systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A quality assessment was performed using an in-house developed grading tool based on components of commonly used grading domains. Data on the electroporation parameters voltage, number of electrodes, inter-electrode distance, active needle length, pulse length/number/protocol/frequency, and pulse interval were extracted. Ablation zone size and temperature data were grouped per parameter. Spearman correlation and linear regression were used to define the correlation with outcome measures. Results: A total of 7661 articles were screened, of which 18 preclinical studies (animal and phantom studies) met the inclusion criteria. These studies were graded as moderate (4/18) and low (14/18) quality. Only the applied voltage appeared to be a significant linear predictor of ablation zone size: length, surface, and volume. The pulse number was moderately but nonlinearly correlated with the ablation zone length. Thermal effects were more likely to occur for higher voltages (≥2000 V), higher number of electrodes, and increased active needle length. Conclusion: Firm conclusions are limited since studies that investigated and precisely reported the influence of electroporation parameters on the ablation zone size and thermal effects were scarce and mostly graded low quality. High-quality studies are needed to improve the predictability of the combined effect of variation in parameter combinations and optimize irreversible electroporation treatment protocols.

Background: As more therapeutic options for pancreatic cancer are becoming available, there is a need to improve outcome prediction to support shared-decision making. A systematic evaluation of prediction models in resectable pancreatic cancer is lacking. Methods: This systematic review followed the CHARMS and PRISMA guidelines. PubMed, Embase and Cochrane Library databases were searched up to 11 October 2017. Studies reporting development or validation of models predicting survival in resectable pancreatic cancer were included. Models without performance measures, reviews, abstracts or more than 10% of patients not undergoing resection in postoperative models were excluded. Studies were appraised critically. Results: After screening 4403 studies, 22 (44 319 patients) were included. There were 19 model development/update studies and three validation studies, altogether concerning 21 individual models. Two studies were deemed at low risk of bias. Eight models were developed for the preoperative setting and 13 for the postoperative setting. Most frequently included parameters were differentiation grade (11 of 21 models), nodal status (8 of 21) and serum albumin (7 of 21). Treatment-related variables were included in three models. The c-statistic/area under the curve values ranged from 0.57 to 0.90. Based on study design, validation Methods and the availability of web-based calculators, two models were identified as the most promising. Conclusion:Although a large number of prediction models for resectable pancreatic cancer have been reported, most are at high risk of bias and have not been validated externally. This overview of prognostic factors provided practical recommendations that could help in designing easily applicable prediction models to support shared decisionmaking.

Review question / Objective: The aim of this study was to review the effect of irreversible electroporation (IRE) parameter settings on the size of the ablation zone and occurrence of thermal effects. Information sources: A search was performed in PubMed (also including MEDLINE), Web of Science, Embase, Institute of Electrical and Electronics Engineers (IEEE) Xplore Digital Library and American Society of Mechanical Engineers (ASME) Digital Collection. Of all conference abstracts of which no full text article was present in the title and abstract search, a web-based search (Google Scholar, ResearchGate, author and co-author name(s) in Embase) was done to investigate whether a full text article was available. A manual search of the reference lists of relevant (included) articles was performed to find articles which were not found by the initial search. The corresponding author was approached by e-mail (in case the contact details were available) when the full text of a relevant abstract (e.g. conference abstract) could not be found to verify whether the results were published as full text. The study was excluded when the full text could not be found or provided.