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.

Experience with Cemented Large Segment Endoprostheses for Tumors

“…For those with a good prognosis, ensuring adjuvant treatment does not interfere with the fixation of the reconstruction could ensure a better outcome, as chemotherapy and radiotherapy may interfere with osteointegration. 7,28,31,32 This theoretical concern, however, has not been documented clinically.…”

Cemented Rotating Hinge Endoprosthesis for Limb Salvage of Distal Femur Tumors

“…For those with better prognosis, avoiding early complications that can interfere with adjuvant treatment and insuring longevity of the construct is of paramount importance. 8,35,36 The use of cemented implants has the additional advantage of immediate stability of the construct, allowing immediate full weightbearing and rehabilitation of the affected limb.…”

Dental Implants in Patients Receiving Chemotherapy

“…Thus, it is suggestive that chemotherapeutic agents have an adverse effect on normal physiological bone turnover, especially osteoblastic activity, and would also be expected to alter fracture-healing and bone-allograft incorporation by these same mechanisms. 18 In the second publication of the study, now turned to a biomechanical and histologic analysis and observing the effects of chemotherapy either preoperatively or postoperatively, Young et al 19 observed that postoperative chemotherapy resulted in less bone formation, but extracortical capsule formation was not inhibited, whereas preoperative chemotherapy did not alter the formation of a new bone. Animal experiments are difficult to translate into a clinical setting, but formation of periimplant connective tissue would be detrimental to the osseointegration of dental implants.…”