title: Fluorescence-guided surgery improves outcome in an orthotopic osteosarcoma nude-mouse model.
abstract: In order to develop a model for fluorescence-guided surgery (FGS), 143B human osteosarcoma cells expressing red fluorescent protein (RFP) were injected into the intramedullary cavity of the tibia in nude mice. The fluorescent areas of residual tumors after bright-light surgery (BLS) and FGS were 10.2 ± 2.4 mm(2) and 0.1 ± 0.1 mm(2) , respectively (p<0.001). The BLS-treated mice and BLS+cisplatinum (CDDP)-treated mice had significant recurrence. In contrast, the FGS mice and FGS+CDDP mice had very little recurring tumor growth. Disease-free survival (DFS) in the BLS-, BLS+CDDP-, FGS-, and FGS+CDDP-treated mice was 12.5%, 37.5%, 75.0%, and 87.5%, respectively. The FGS-treated mice had a significantly higher DFS rate than the BLS-treated mice (p=0.021). The FGS+CDDP-treated mice had significantly higher DFS rate than the BLS+CDDP-treated mice (p=0.043). Although chemotherapy significantly reduced multiple metastases (p=0.033), there was no significant correlation between FGS and lung metastasis. FGS significantly reduced the recurrence of the primary tumor but did not reduce lung metastasis. The combination of FGS and adjuvant CDDP reduced tumor recurrence and prevented multiple metastases. FGS and adjuvant chemotherapy should be performed as early as possible in the disease to prevent both recurrence and metastatic development.
authors.affiliation: AntiCancer, Inc., San Diego, CA; Department of Surgery, University of California, San Diego, San Diego, CA; Department of Orthopedic Surgery, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Ishikawa, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Miwa
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Hiroshima
authors.forename: Shuya
authors.initials: S
authors.lastname: Yano
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Matsumoto
authors.forename: Fuminari
authors.initials: F
authors.lastname: Uehara
authors.forename: Mako
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kimura
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Hayashi
authors.forename: Michael
authors.initials: M
authors.lastname: Bouvet
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tsuchiya
authors.forename: Robert M
authors.initials: RM
authors.lastname: Hoffman
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000401:mortality / Q000601:surgery*; D002945:Cisplatin / Q000627:therapeutic use; D004195:Disease Models, Animal; D005260:Female; D005453:Fluorescence; D008175:Lung Neoplasms / Q000556:secondary; D008819:Mice, Nude; D012516:Osteosarcoma / Q000401:mortality / Q000601:surgery*; D016896:Treatment Outcome
chemical_list: D002945:Cisplatin
keywords: RFP; chemotherapy; cisplatinum (CDDP); fluorescence-guided surgery; orthotopic mouse model; osteosarcoma