Interstitial laser thermotherapy of adenocarcinoma transplanted into rat liver

Objective: To examine the effect of different temperatures and exposure times in interstitial laser thermotherapy. Design: Controlled laboratory study. Setting: University hospital, Sweden. Material: 48 male Wistar FU rats with dimethylhydrazine-induced adenocarcinoma transplanted into the liver. Intervention: Treatment was given with an Nd:YAG laser and a feedback system for temperature regulation. Light was delivered into the centre of the turnout and the feedback thermistor probe was placed 3 mm from the tumour margin. Rats were treated at steady-state temperatures at the feedback thermistor of 43, 46, or 50°C for 30 minutes, and at a steady-state temperature of 46°C at the feedback thermistor also for 10 and 20 minutes. Main outcome measurement: Tumour control as assessed 6 days after treatment using light microscopical examination including immunohistochemical determination of bromodeoxyuridine (BrdU) incorporation into DNA as a measure of cell viability. Results: Complete tumour necrosis was achieved in all rats treated for 30 minutes, in 6/8 rats treated for 10 minutes and in 6/8 rats treated for 20 minutes at 46°C. During steady-state thermotherapy, temperatures at the tumour margin were about 11°higher than at the feedback thermistor (range 54-61°C). The surrounding liver tissue also became necrotic so that the total necrosis volume exceeded the pretreatment tumour volume. Conclusion: Interstitial laser thermotherapy at temperatures ranging from 54-61°C at the tumour margin ensures total necrosis of a transplanted rat liver carcinoma provided that treatment is given for 30 minutes

Angiogenesis inhibitor TNP-470 augments the effect of repeated arterial ischemia on growth but does not affect take in a rat liver tumor model

Transient hepatic arterial occlusion causes necrosis in solid hepatic tumors in the rat, but regrowth of tumor cells and capillaries takes place from the tumor periphery. It was therefore considered of interest to combine this treatment with the angiogenesis inhibitor TNP-470 (therapeutic model). Wistar rats with a dimethylhydrazine-induced adenocarcinoma implanted into the liver received one of the following treatments: TNP-470 + transient hepatic ischemia, transient hepatic ischemia alone, TNP-470 alone or sham solution alone. Rats were sacrificed one week after the start of treatment. In addition, we investigated if TNP-470 decreases the risk of tumor take in the liver after intraportal injection of viable tumor cells (adjuvant study). Transient hepatic ischemia combined with TNP-470 gave a smaller increase in tumor volume than transient hepatic ischemia (p < 0.01), TNP-470 (p < 0.001) alone or no treatment (p < 0.001). Transient hepatic ischemia or TNP-470 caused a significant suppression of tumor growth when compared to controls (p < 0.01 in both cases). In the adjuvant study, TNP-470 caused retardation of tumor growth (p < 0.01 as compared to controls) but did not affect tumor number. It is concluded that TNP-470 suppressed tumor growth, both alone and in combination with transient hepatic ischemia, but did not affect take of tumor