title: Effect of cisplatin chemotherapy on extracortical tissue formation in canine diaphyseal segmental replacement.
abstract: The reconstruction of large bone and joint defects after the resection of malignant tumors remains a major challenge. Chemotherapy has significantly lowered the risk of metastasic disease, but complications associated with reconstructive techniques continue to result in late morbidity. In the present study, biomechanical torsion testing, gait analysis, and histomorphometric and scanning electron microscopic evaluations of 24 dogs were used to examine the effects of preoperative and postoperative administration of cisplatin on the biologic fixation of a porous-coated segmental replacement prosthesis. The chemotherapy consisted of four cycles of cisplatin administered at a dosage of 75 mg/m2 preoperatively or postoperatively. The healing was enhanced by use of an autogenous corticocancellous bone graft. The graft was placed evenly around the prosthesis and the adjacent femoral cortex. Mechanical analyses of torsional stiffness, yield strength, and maximum strength revealed no statistically significant differences between the groups at 12 weeks. Such lack of difference was mainly due to the penetration of highly organized fibrous tissue into the porous surface; this provided strong fixation of the implant to bone even in the absence of bone ingrowth. Although bone ingrowth into the prostheses was not affected, electron microscopic, histomorphometric, and radiologic analyses showed a clear difference in the formation of new bone around the prosthesis. Preoperative chemotherapy did not alter the formation of new bone, but specimens from animals treated postoperatively with cisplatin showed significantly less bone graft resorption and less new bone formation. Hence, the effect of cisplatin administration caused only a temporary delay, not a permanent effect, on extracortical capsule formation. The formation of extracortical bone and soft tissue might prevent debris-incised osteolysis and, therefore, prevent late complications by forming a tight capsule around the bone-prosthetic interface.
authors.affiliation: Department of Orthopaedic Surgery, Johns Hopkins University, Baltimore, Maryland 21205-2196, USA.
authors.forename: D R
authors.initials: DR
authors.lastname: Young
authors.forename: L Y
authors.initials: LY
authors.lastname: Shih
authors.forename: M G
authors.initials: MG
authors.lastname: Rock
authors.forename: F J
authors.initials: FJ
authors.lastname: Frassica
authors.forename: P
authors.initials: P
authors.lastname: Virolainen
authors.forename: E Y
authors.initials: EY
authors.lastname: Chao
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001696:Biomechanical Phenomena; D001846:Bone Development / Q000187:drug effects*; D002945:Cisplatin / Q000494:pharmacology*; D018483:Diaphyses / Q000187:drug effects / Q000502:physiology / Q000601:surgery / Q000648:ultrastructure; D004285:Dogs; D005269:Femur / Q000187:drug effects* / Q000502:physiology / Q000601:surgery / Q000648:ultrastructure; D020007:Implants, Experimental; D008297:Male; D016348:Osseointegration / Q000187:drug effects*; D019919:Prosthesis Implantation; D013314:Stress, Mechanical; D016474:Weight-Bearing / Q000502:physiology
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin