[Pulsed radiofrequency ablation using perfused needle applicators in an in vitro trial on bovine liver]. / Getaktete Dreifachapplikation mit perfundierten Nadelapplikatoren bei Radiofrequenzablation: In-vitro-Versuch an der Rinderleber.

Intermittent energy application seems to have positive effects in achieving necrotic zones. We analyzed different pulse periods (PPs) to optimize this method. A radiofrequency alternating current was delivered via a triple-needle applicator (3 cm distance of each needle) introduced into freshly procured bovine liver. The open applicator system was constantly perfused with physiological NaCl solution (3×80 ml/h, power output was constant 90 W). Radiofrequency current was fed to the individual needle in turn of varying PPs (1, 2, 5, and 7 s) over 15 min. Each experimental run comprised a total of 30 applications and temperature was recorded over time. The largest necrotic diameters were found at PP 1 s (relevant: shortest axial diameter/D in the center of the lesion: 9.27 cm, SD±0.97 cm) (PP 2 s D=8.65 cm, SD±0.95 cm, p=0.021; PP 5 s D=8.35 cm, SD±0.95 cm, p=0.001; PP 7 s D=8.18 cm, SD±0.79 cm, p=0.0001). Neither doubling the perfusion rate nor raising the concentration of the perfusion liquid led at PP 1 s to increased necrotic diameters (p=0.82). Our study shows that reducing the PP to 1 s of an open perfused intermittent radiofrequency ablation system produces significantly larger coagulation volumes in explanted liver tissue reaching necrotic diameters over 9 cm. Neither doubling perfusion rates nor higher concentrated perfusion liquid increase necrotic diameters.

Hepatic transit time of an echo enhancer: an indicator of metastatic spread to the liver.

OBJECTIVE: Can sonographic measurements of the transit time of an echo enhancer from the hepatic artery to the hepatic vein discriminate between patients with and without liver metastases? METHOD: The hepatic transit time (hepatic artery to hepatic vein delay) of an echo enhancer (Optison) was measured in pulse inversion mode on the basis of time intensity curves (TIC) in patients with gastrointestinal tumours with proven liver metastases and in patients without liver metastases. RESULTS: Sixty-four patients (46 males, 18 females, mean age 61 +/- 13 years) were admitted to the study. Fourteen patients had metastatic growth in the liver with a primary tumour in situ (group A). Fourteen patients had liver metastases following primary tumour resection (group B). Twenty-eight patients had a known primary tumour but no liver metastases (group C), and eight patients had neither liver symptoms nor a primary tumour (group D). The mean hepatic transit time in patients with liver metastases was 6.6 +/- 1.8 s in group A and 6.7 +/- 1.7 s in group B, whereas in patients without liver metastases it was significantly longer; namely, 15.7 +/- 4.4 s in group C and 15.0 +/- 2.0 s in group D (P < 0.001). The transit times in all patients with liver metastases were < or = 10 s, while in all patients without metastases except for four the times were > or = 12 s and one of the four had already developed liver metastases on early follow-up. CONCLUSIONS: Measurement of the hepatic transit time permits discrimination of patients with and without liver metastases.

Percutaneous US-guided radiofrequency ablation with perfused needle applicators: improved survival with the VX2 tumor model in rabbits.

PURPOSE: To evaluate survival, metastases, tumor necrosis, and prediction of local recurrence after percutaneous ultrasonographically (US) guided radiofrequency (RF) thermal ablation with electrodes perfused continuously with isotonic saline. MATERIALS AND METHODS: VX2 liver tumors were implanted in 31 rabbits according to a standardized protocol. After 21 days, 16 animals were treated percutaneously with RF ablation. Four animals died of complications related to anesthesia, and 12 animals were evaluated. All animals were followed for 110 days and monitored with computed tomography (CT) and US at 1, 7, and 30 days. A control group of 15 animals did not receive treatment. Autopsy was performed at the end of scheduled follow-up or immediately after death. For survival analysis, the Kaplan-Meier method was used; for nominal data, the Fisher exact test was used. RESULTS: In comparison to controls, animals in the treatment group showed significantly prolonged survival (P <.001). Eight of 12 animals (67%) treated with RF ablation survived to 110 days, while none of the controls did so. Metastases developed in all controls (100%) and in eight of 12 treated animals (67%) (P =.001). In comparison with controls, animals that developed metastases despite treatment also showed significantly prolonged survival (P =.02). Local recurrence was observed in three of 12 animals (25%) in the treatment group. CT and US performed 1 week after treatment did not allow prediction of local recurrence. CONCLUSION: RF ablation of liver tumors with perfused needle applicators prolongs survival in the VX2 rabbit liver tumor model, regardless of whether complete remission is achieved. In comparison with controls, RF ablation results in a lower frequency of metastases.

Activation of tumor-specific T lymphocytes by radio-frequency ablation of the VX2 hepatoma in rabbits.

Radio-frequency ablation (RFA) is used as a minimally invasive treatment for inoperable hepatic tumors. Immunological reactions secondary to RFA may play a role in the observed tumor control. In our study, the VX2 carcinoma was implanted into the liver of rabbits. After 3 weeks, tumors were treated with RFA or were left untreated. Peripheral blood lymphocytes were harvested before tumor implantation, 2 weeks postoperatively and at 2-week intervals thereafter. T cells were stimulated with lysates of either tumor tissue or nontumorous liver loaded on autologous antigen-presenting cells and their stimulation index was determined by [(3)H]thymidine incorporation. A 3-fold increase over background or controls was considered significant. Stimulation with phytohemagglutinin served as a positive control. The animals were necropsied, and liver and tumor tissue were analyzed immunohistologically for T-cell infiltration. T cells from tumor-bearing (n = 9) and RFA-treated (n = 11) animals were investigated in a follow-up study. The mean postoperative observation was 45 days. All of the 11 RFA-treated animals exhibited circulating T cells activated specifically toward tumor antigens throughout the observation period, which was accompanied by dense T-cell infiltration. In contrast, T cells of untreated tumor-bearing rabbits showed no reaction and only sparse T cell infiltration. We concluded that RFA induces a tumor-specific T-cell reaction in the otherwise unreactive tumor-bearing host, apparently overcoming immune tolerance and leading to the presentation of otherwise cryptic tumor antigens. Therefore, in addition to destroying tumor tissue, RFA induces an immune response against tumor antigens that may be exploited in multimodal antitumor strategies.