title: Synergistic effect of interstitial laser coagulation and doxorubicin in a murine tumor recurrence model of solitary colorectal liver metastasis.
abstract: BACKGROUND
  Interstitial laser coagulation (ILC) is gaining acceptance for treatment of unresectable colorectal liver metastases. However, local recurrence rates are still high. To overcome this problem, we investigated the potential of additional systemic therapy after ILC in a murine model.
  
  
  METHODS
  Single C26 colon carcinoma nodules (approximately 1 mm3) expressing firefly luciferase were implanted in the left liver lobe of 32 BALB/c mice. Seven days after implantation, tumors were treated with either ILC alone (neodymium-yttrium aluminum garnet; 6 W/cm; 800 J/cm) or ILC followed by 1 mg/kg of doxorubicin intravenously. Controls received either doxorubicin alone or sham treatment. Tumor load was measured by in vivo bioluminescent imaging.
  
  
  RESULTS
  Solitary colorectal liver metastases developed over 7 days after tumor implantation in the liver. Extrahepatic disease was not observed. The ILC dose was set to ablate the liver metastases with recurrent tumor growth in 9 of 16 mice after 7 days. After ILC plus doxorubicin, complete tumor destruction occurred without recurrence (0 of 14). Sham treatment or treatment with doxorubicin alone showed an exponential increase in tumor load.
  
  
  CONCLUSIONS
  A murine tumor recurrence model after local ablative treatment of solitary liver metastasis was developed. The combination of ILC and doxorubicin had a strong synergistic effect that led to complete tumor remission in all animals treated.
authors.affiliation: Department of Surgery, University Medical Center Utrecht, P. O. Box 85500, 3508 GA Utrecht, The Netherlands.
authors.forename: Liesbeth M
authors.initials: LM
authors.lastname: Veenendaal
authors.forename: Richard
authors.initials: R
authors.lastname: van Hillegersberg
authors.forename: Niels
authors.initials: N
authors.lastname: Smakman
authors.forename: Jarmila D W
authors.initials: JD
authors.lastname: van der Bilt
authors.forename: Paul J
authors.initials: PJ
authors.lastname: van Diest
authors.forename: Onno
authors.initials: O
authors.lastname: Kranenburg
authors.forename: Inne H M
authors.initials: IH
authors.lastname: Borel Rinkes
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000473:pathology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage*; D007150:Immunohistochemistry; D017075:Laser Coagulation; D008113:Liver Neoplasms / Q000401:mortality / Q000473:pathology / Q000556:secondary* / Q000628:therapy*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009364:Neoplasm Recurrence, Local; D011897:Random Allocation; D016019:Survival Analysis
chemical_list: D000970:Antineoplastic Agents; D004317:Doxorubicin