Experimental study of paraplegia caused by spinal tumors: an animal model of spinal tumors created by transplantation of VX2 carcinoma.
BACKGROUND
Little is known about the mechanism of the paraplegia produced by metastatic spinal tumors, although the quality of life of patients with paraplegia caused by malignant tumors depends to a great extent on treatment of the paraplegia. We previously established an experimental model of malignant femoral tumors by transplanting VX2 carcinoma into the femur, and we have reported the efficacy of chemical embolic therapy, radiotherapy and hyperthermal therapy in treating the tumors in the model.


OBJECTIVE
The purpose of the present study was to establish an animal model of metastatic spinal tumors by transplanting VX2 carcinoma into a pedicle and to analyze the mechanism of the paraplegia produced by metastatic spinal tumors.


METHODS
An experimental study.


METHODS
VX2 carcinoma that had been successively transplanted to the thigh muscles of Japanese White rabbits in the Department of Orthopaedic Surgery of Kyorin University School of Medicine was used. The third lumbar vertebra of 37 healthy rabbits was exposed, and a piece of VX2 carcinoma was transplanted into a hole created in the pedicle with an air drill after transplantation. The animals were examined every other day. As soon as paraplegia developed, the animals were sacrificed, and the axial localization of the tumor was evaluated based on the surgical staging of the spinal tumor (SSST classification by Tomita). Roentgenographic, histological and angiographic studies were also performed.


RESULTS
Twenty-two rabbits (60%) had paraplegia at the time of the final examination. Seventeen of them had complete paraplegia, and the other five had incomplete paraplegia. The average interval until incomplete paraplegia developed was 18.4+/-4.3 days, and the average interval until complete paraplegia developed was 30.0+/-4.3 days. The average proportion of the diameter of the spinal canal occupied by the tumor was 37.2+/-4.9% in the incomplete cases, and 70.6% in the complete cases. The radiographs revealed an osteolytic area in the pedicle and posterior border of the third lumbar vertebra in the rabbits with complete paraplegia, but no osteolytic areas were detected in the rabbits with incomplete paraplegia. According to the SSST classification, the lesions of all of the rabbits with paraplegia were classified as stage IV. Pathological studies revealed that the spinal cord generally exhibited degenerative change, especially at the site of tumor compression. No tumor cells had invaded the spinal cord. Microangiography showed a marked reduction in blood vessels in the gray matter of the spinal cord in the complete paraplegia in comparison with incomplete paraplegia.


CONCLUSIONS
Our method succeeded in establishing a model of metastatic spinal tumors, because the natural history of the disease, including the anatomical location of the tumors and the imaging findings, was similar to the natural history in clinical cases. This model was useful for elucidating the pathogenetic mechanism of the paraplegia caused by metastatic spinal tumors.
Takahashi
Masahito
M
Department of Orthopaedic Surgery, School of Medicine, Kyorin University, 6-20-2 Shinkawa Mitaka-shi, Tokyo 181-8611, Japan. masahit@par.odn.ne.jp
Ogawa
Jun
J
Kinoshita
Yoshiaki
Y
Takakura
Motoki
M
Mochizuki
Kazuo
K
Satomi
Kazuhiko
K
D000818:Animals; D004195:Disease Models, Animal; D008297:Male; D009362:Neoplasm Metastasis / Q000473:pathology / Q000503:physiopathology; D009368:Neoplasm Transplantation; D010264:Paraplegia / Q000209:etiology* / Q000503:physiopathology*; D011817:Rabbits; D013125:Spinal Neoplasms / Q000150:complications* / Q000473:pathology*