Browsing by Author "Villas, Carlos"

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    Clinical Outcome and Histological Findings After Induced Leakage of PMMA Loaded With Methotrexate and Cisplatin During Vertebroplasty: Experimental Model in Pigs
    (2021) Silva, Álvaro; Llombart, Rafael; Gallegos, Marcela; Villas, Carlos; Olmos, Matías
    Study design: Animal experimental model. Objective: To study the clinical behavior and histological changes in the spinal cord, nerve roots and perivertebral muscles of the spine after induced leakage of polymethylmethacrylate (PMMA) loaded with antiblastic drugs during vertebroplasty in an animal model of pigs. Methods: We performed vertebroplasty on 25 pigs. The animals were divided into 3 groups: vertebroplasty with PMMA alone (control group), vertebroplasty with PMMA loaded with methotrexate (MTX) and vertebroplasty with PMMA loaded with cisplatin (CYS). At 2 vertebral levels, epidural and prevertebral, massive cement leaks were induced. Animals were evaluated daily. Two weeks later, the pigs were sacrificed, and the tissues that came in contact with the cement were analyzed. Results: The clinical results for each of the groups were reported. The control group had no clinical alterations. In the MTX group, 2 pigs died before 1 week due to pneumonitis. In the CYS group, 4 animals had motor impairment, and 3 of the 4 had paraplegia. The histological results were as follows: the control and MTX groups showed synovial metaplasia, inflammatory reaction, crystal deposits, and giant cell reaction in the dura mater and muscle and all the animals in the CYS group had spinal cord and muscular necrosis. Conclusions: Massive cement leak after vertebroplasty with PMMA loaded with cisplatin is extremely toxic to the spinal cord and muscles around the spine. Therefore, its use cannot be recommended for the treatment of vertebral metastases. Using PMMA loaded with methotrexate seems to be a safe procedure, but further research is needed.
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    Local and systemic diffusion of antineoplastic drugs following vertebroplasty using acrylic cement mixed with cisplatin or methotrexate: experimental study in pigs
    (Springer, 2017) Llombart-Blanco, Rafael; Villas, Carlos; Silva, Álvaro; Aldaz, Azucena; Navarro, Iñigo; Forteza, Jeronimo; Matías Alfonso; Alfonso, Matías; Algarra, Salvador Martin
    PURPOSE: To determine the efficacy of cisplatin- or methotrexate-containing acrylic cement for local and systemic antineoplastic drug diffusion. Among the uses of acrylic cement or Polymethylmethacrylate (PMMA), there is the possibility to employ it as vehicle for drug diffusion. This capability is of interest in the treatment of pathological fractures: The curative effects of the cement (cytotoxicity of the monomer and increased temperature) are added to the antineoplastic effect of the drugs. METHODS: In the experimental study, two groups of ten pigs underwent vertebroplasty using cement mixed with 500 mg of powder cisplatin or 1000 mg of powder methotrexate. Vertebroplasty was performed in two non-consecutive lumbar vertebrae with bipedicular cement injection. Transpedicular bone biopsy was performed weekly to measure levels of antineoplastic agent in bone tissue and blood plasma. Cisplatin was studied by atomic absorption spectrometry and methotrexate by fluorescence polarization immunoassay. Renal and hepatic function and blood analysis were performed weekly. RESULTS: Cisplatin and methotrexate levels were found in bone tissue at more than 5 weeks following surgery. The cisplatin peak occurred at week 3 (mean 1269 μg/g bone) and the methotrexate peak at week 1 (mean 862.76 μg/g bone). Plasma drug levels were found 72 h after surgery, with a peak at 24 h for cisplatin (mean 0.23 μmol/L) and at 30 min for methotrexate (mean 0.92 μmol/L). None of the animals died during the study. Animals with intracanal cement leaks showed no neurological involvement. Renal, hepatic and hemogram studies remained within normal limits. CONCLUSIONS: There is local diffusion of antineoplastic agents from the cement to bone and plasma. We found methotrexate and cisplatin levels in bone at up to 5 weeks, comparable to previous in vitro reports. At the doses administered, there were no cases of myelosuppression, hepatotoxicity, or nephrotoxicity.

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