In some conditions of high intensity, IRE can produce sufficient heating to induce "white zone" thermal coagulation. While this can be useful in some settings to increase tumor destruction, further characterization of the thermal profile created with clinical electrodes and energy parameters is therefore needed to better understand the best ways to avoid unintended damage when ablating near thermally sensitive critical structures.

PurposeThe miniature biodegradable implant siG12D-LODER™ was inserted into a tumor and released a siRNA drug against KRAS(G12D) along four months. This novel siRNA based drug was studied, in combination with chemotherapy, as targeted therapy for Locally Advanced Pancreatic Cancer (LAPC).MethodsAn open-label Phase 1/2a study in the first-line setting of patients with non-operable LAPC was initiated. In this study patients were assigned to receive a single dose of siG12D-LODERs, in three escalating dose cohorts (0.025mg, 0.75mg and 3.0mg). Gemcitabine was given on a weekly basis, following the siG12D-LODERTM insertion, until disease progression. The recommended dose was further examined with modified FOLFIRINOX. The follow up period was eight weeks and survival until death.ResultsFifteen patients with LAPC were enrolled. Among the 15 treated patients, the most frequent adverse events observed were grade 1or 2 in severity (89%); five patients experienced serious adverse events (SAEs). In 12 patients analyzed by CT scans, none showed tumor progression, the majority (10/12) demonstrated stable disease and two showed partial response. Decrease in tumor marker CA19-9 was observed in 70% (7/10) of patients. Median overall survival was 15.12 months; 18 month survival was 38.5%.ConclusionsThe combination of siG12D-LODER™ and chemotherapy is well tolerated, safe and demonstrated a potential efficacy in patients with LAPC. NCT01188785

US findings in the acute period after IRE are dynamic and evolve. The ablation zone can be best predicted by measuring the external hyperechoic rim that forms 90-120 minutes after ablation. This rim is possibly attributable to evolving hemorrhagic infiltration via widened sinusoids.

).q RSNA, 2013 Purpose:To study the effects of the surrounding electrical microenvironment and local tissue parameters on the electrical parameters and outcome of irreversible electroporation (IRE) ablation in porcine muscle, kidney, and liver tissue. Materials and Methods:Animal Care and Use Committee approval was obtained, and National Institutes of Health guidelines were followed. IRE ablation (n = 90) was applied in muscle (n = 44), kidney (n = 28), and liver (n = 18) tissue in 18 pigs. Two electrodes with tip exposure of 1.5-2 cm were used at varying voltages (1500-3000 V), pulse repetitions (n = 70-100), pulse length (70-100 µsec), and electrode spacing (1.5-2 cm). In muscle tissue, electrodes were placed exactly parallel, in plane, or perpendicular to paraspinal muscle fibers; in kidney tissue, in the cortex or adjacent to the renal medulla; and in liver tissue, with and without metallic or plastic plates placed 1-2 cm from electrodes. Ablation zones were determined at gross pathologic (90-120 minutes after IRE) and immunohistopathologic examination (6 hours after) for apoptosis and heat-shock protein markers. Multivariate analysis of variance with multiple comparisons and/or paired t tests and regression analysis were used for analysis. Results:Mean (6 standard deviation) ablation zones in muscle were 6.2 cm 6 0.3 3 4.2 cm 6 0.3 for parallel electrodes and 4.2 cm 6 0.8 3 3.0 cm 6 0.5 for in-plane application. Perpendicular orientation resulted in a cross-shaped zone. Orientation significantly affected IRE current applied (28.5-31.7A for parallel, 29.5-39.7A for perpendicular; P = .003). For kidney cortex, ovoid zones of 1.5 cm 6 0.1 3 0.5 cm 6 0.0 to 2.5 cm 6 0.1 3 1.3 cm 6 0.1 were seen. Placement of electrodes less than 5 mm from the medullary pyramids resulted in treatment effect arcing into the collecting system. For liver tissue, symmetric 2.7 cm 6 0.2 3 1.4 cm 6 0.3 coagulation areas were seen without the metallic plate but asymmetric coagulation was seen with the metallic plate. Conclusion:IRE treatment zones are sensitive to varying electrical conductivity in tissues. Electrode location, orientation, and heterogeneities in local environment must be considered in planning ablation treatment.q RSNA, 2013 Supplemental material: http://radiology.rsna.org/lookup /suppl

Predictable zones of tissue destruction can be achieved for irreversible electroporation. Ablation dimensions are sensitive to multiple parameters, suggesting that precise technique and attention to detail will be particularly important when using this modality.