Thermo-chemo-radiotherapy for advanced bile duct carcinoma

Complete resection of the bile duct carcinoma is sometimes difficult by subepithelial spread in the duct wall or direct invasion of adjacent blood vessels. Nonresected extrahepatic bile duct carcinoma has a dismal prognosis, with a life expectancy of about 6 mo to 1 year. To improve the treatment results of locally advanced bile duct carcinoma, we have been conducting a clinical trial using regional hyperthermia in combination with chemoradiation therapy.

Eight patients complaining of obstructive jaundice with advanced extrahepatic bile duct underwent thermo-chemo-radiotherapy (TCRT). All tumors were located in the upper bile duct and involved hepatic bifurcation, and obstructed the bile duct completely. Radiofrequency capacitive hyperthermia was administered simultaneously with chemotherapeutic agents once weekly immediately following radiotherapy at 2 Gy. We administered heat to the patient for 40 min after the tumor temperature had risen to 42 degrees C. The chemotherapeutic agents employed were cis-platinum (CDDP, 50 mg/m(2)) in combination with 5-fluorouracil (5-FU, 800 mg/m(2)) or methotrexate (MTX, 30 mg/m(2)) in combination with 5-FU (800 mg/m(2)). Number of heat treatments ranged from 2 to 8 sessions. The bile duct at autopsy was histologically examined in three patients treated with TCRT.

In respect to resolution of the bile duct, there were three complete regression (CR), two partial regression (PR), and three no change (NC). Mean survival was 13.2+/-10.8 mo (mean+/-SD). Four patients survived for more than 20 mo. Percutaneous transhepatic biliary drainage (PTBD) tube could be removed in placement of self-expandable metallic stent into the patency-restored bile duct after TCRT. No major side effects occurred. At autopsy, marked hyalinization or fibrosis with necrosis replaced extensively bile duct tumor and wall, in which suppressed cohesiveness of carcinoma cells and degenerative cells were sparsely observed.

Although the number of cases is rather small, TCRT in the treatment of locally advanced bile duct carcinoma is promising in raising local control and thus, long-term survival.