Endohyperthermia - Experimental Evaluation of a New Therapeutic Approach for Treatment of Biliary Carcinoma

Background and Study Aims: To improve the prognosis of patients with unresectable, locally advanced bile duct carcinoma, new treatment strategies need to be evaluated. Hyperthermia has been successfully applied as part of multimodal therapy in esophageal and rectal carcinoma. We performed in-vitro and in-vivo experiments with a new intraluminal hyperthermia system in the biliary tract.

Methods: A radiofrequency system (13.56 MHz, Endoradiotherm XERT-200A; Olympus Optical Co., Tokyo, Japan) was used with a special intraluminal microelectrode (diameter 4.5 mm, length 40 mm) covered by a silicone balloon with cooling water and a large counter electrode for focusing the electromagnetic field around the electrode. The heating capacity of the endohyperthermia unit was examined in vitro in a muscle-equivalent phantom (agar 4 %), in isolated livers of pigs and cows, as well as in vivo in anesthetized sheep. Continuous thermometry was done with thermosensors at the applicator surface, and with multichannel thermocouple probes in the environment of the applicator.

Results: Endohyperthermia induced a homogeneous heating of the phantom and the isolated liver bile duct preparation to a temperature ≥ 40 °C in an area at least 10 mm in depth. After placement of the applicator into the common bile duct of anesthetized sheep, endohyperthermia led to a consistent and repeatable heating of the surrounding tissue to 40.5 ± 0.5 °C at 1cm distance, and 39.9 ± 0.7 °C at 2 cm distance. Blood pressure, heart rate, and systemic temperature did not change in vivo. Histological examination of the bile duct showed superficial mucosal necrosis (depth 100 - 200 μm), microvascular damage with petechiae, congestion and edema of the bile duct wall and adventitia after hyperthermia treatment in vivo.

Conclusions: The intraluminal endohyperthermia system produces consistent and repeatable heating of the surrounding tissue. Since effective thermal power can reach a depth of up to 2 cm, tumors may also be heated adequately.

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