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Background and Study Aims: Radiofrequency ablation (RFA) is an accepted method of tissue destruction for solid organ tumors. Endoscopic ultrasound (EUS)-guided RFA has been used for lesions in the pancreas and liver, but there is limited experience of lymph node ablation using EUS-guided RFA. The aim of this study was to determine feasibility and safety of prototype EUS-guided RFA of mediastinal lymph nodes., Methods: This was an endoscopic experimental feasibility study in a porcine model. After EUS-guided puncture of targeted lymph nodes, the stylet of a 19-G needle was replaced by a prototype RFA probe. RFA was performed by ERBE generator (bipolar settings: 10 watts, effect 2, 2 minutes). The animals were euthanized, and the targeted lymph nodes were identified and removed for histology and measurement of the effect achieved., Results: A total of 18 mediastinal lymph nodes were ablated (mean size 20.8 ± 6.6  mm in the long axis). The average length of exposed probe was 10.0 ± 3.0 mm. The mean length and diameter of necrosis was 9.8 ± 3.6  mm and 5.5 ± 1.6  mm, respectively. Linear regression comparing needle length with necrosis diameter revealed a coefficient gradient of r = 0.92 (P = 0.0001). With EUS-RFA a mean of 17.6 ± 10.3 % (range 8.0 % - 53.2 %) of the respective lymph node area was ablated. No complications (i. e. hemodynamic instability, local bleeding, tissue damage) occurred during the procedure. Technical problems included stripping of the probe by the EUS needle and bending of the tip of the probe., Conclusions: EUS-RFA of lymph nodes was performed safely and successfully using a prototype EUS-compatible probe. This method may have the potential for future use in patient care., (© Georg Thieme Verlag KG Stuttgart · New York.)