Bone turnover and microdamage are impacted by skeletal metastases which can contribute to increased fracture risk. Treatments for metastatic disease may further impact bone quality. This study aimed to establish an understanding of microdamage accumulation and load to failure in healthy and osteolytic vertebrae following cancer treatment (stereotactic body radiotherapy (SBRT), zoledronic acid (ZA), or docetaxel (DTX)). Forty-two 6-week old athymic female rats (Hsd:RH-Foxn1rnu, Envigo) were studied; 22 were inoculated with HeLa cervical cancer cells through intracardiac injection (day 0). Animals were randomly assigned to four groups: untreated (healthy=5, osteolytic=6), SBRT on day 14 (healthy=6, osteolytic=6), ZA on day 7 (healthy=4, osteolytic=5), and DTX on day 14 (healthy=5, osteolytic=5). Animals were euthanized on day 21. L1-L3 motion segments were compression loaded to failure and force-displacement data recorded. T13 vertebrae were stained with BaSO. 4. and µCT imaged (90kVp, 44uA, 4.9µm) to visualize microdamage location and volume. Damage volume fraction (DV/BV) was calculated as the ratio of BaSO. 4. to bone volume. Differences in mean load-to-failure were compared using three-way ANOVA (disease status, treatment, cells injected). Differences in mean DV/BV between treatment groups were compared using one-way ANOVA. Treatment had a significant effect on load-to-failure (p=0.004) with ZA strengthening the healthy and osteolytic vertebrae. Reduced strength post SBRT seen in the metastatic (but not the healthy) group may be explained by greater tumor involvement secondary to higher cell injection concentrations. Untreated metastatic samples had higher DV/BV (16.25±2.54%) compared to all treatment groups (p<0.05) suggesting a benefit of treatment to bone quality. Focal and systemic cancer treatments were shown to effect load-to-failure and microdamage accumulation in healthy and osteolytic vertebrae. Developing a better understanding of how treatments effect bone quality and mechanical stability is critical for effective management of patients with
Vertebral metastases are the most common type of malignant lesions of the spine. Although this tumour is still considered incurable and standard treatments are mainly palliative, the standard approach consists in surgical resection, which results in the formation of bone gaps. Hence, scaffolds, cements and/or implants are needed to fill the bone lacunae. Here, we propose a novel approach to address
Photodynamic therapy (PDT) uses the strong cytotoxicity of singlet oxygen and hyperthermia produced by irradiating excitation light on a photosensitizer. The phototoxic effects of indocyanine green (ICG) and near-infrared light (NIR) have been studied in different types of cancer cells. Plasma proteins bind strongly to ICG, followed by rapid clearance by the liver, resulting in no tumor-selective accumulation after systemic administration. Kimura et al. have proposed using a novel nanoparticle labeled with ICG (ICG-lactosome) that has tumor selective accumulation owing to enhanced permeability and retention (EPR) effect. In this study, we investigated the efficacy of PDT using ICG-lactosome and NIR for a bone metastatic mouse model of breast cancer. Cells from the human breast cancer cell line, MDA-MB-231 were injected into the right tibia of 26 anesthetized BALB/C nu/nu mice at a concentration. The mice were then randomly divided into three groups: the PDT group (n = 9), the laser (laser irradiation only) group (n = 9), and the control group (n = 8). PDT was performed thrice (7, 21, 35 days after cell inoculation) following ICG-lactosome administration via the tail vein 24 hours before irradiation. The mice were percutaneously irradiated with an 810-nm medical diode laser for 10 min. In the laser group, mice were irradiated following saline administration 24 hours before irradiation. Radiographic analysis was performed for 49 days after cell inoculation. The area of osteolytic lesion was quantified. The right hind legs of 3 mice were amputated 24 hours after the third treatment. Histological analysis was performed using hematoxylin-eosin staining and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining of sagittal sections. The data was analyzed using Tukey-Kramer post-hoc test. P-value of <0.05 was considered significant. X-ray on day 49 of the three groups are considered. The area of osteolytic lesion in the PDT group (7.9 ± 1.2 mm. 2. : mean ± SD) was significantly smaller than that of the control (11.4 ± 1.4 mm. 2. ) and laser (11.9 ± 1.2 mm. 2. ) groups. In histological findings, we observed many TUNEL-positive cells in the metastatic tissue 24 hours after PDT. In the control and laser groups, TUNEL-positive cells were occasionally observed. We have previously reported the effect of ICG-lactosome-enhanced PDT on the cytotoxicity of human breast cancer cells in vitroand on the delay of paralysis in a rat spinal metastasis model. In this study, we demonstrated the inhibitory effect of ICG-lactosome-enhanced PDT on bone destruction caused by human breast cancer cells in vivo. This PDT induced apoptosis and necrosis in the tumor cells. Intralesional resection is often performed for
Summary. This is the first ever study to report the successful elimination of malignant cells from salvaged blood obtained during metastatic spine tumour surgery using a leucocyte depletion filter. Introduction. Catastrophic bleeding is a significant problem in metastatic spine tumour surgery (MSTS). However, intaoperative cell salvage (IOCS) has traditionally been contraindicated in tumour surgery because of the theoretical concern of promoting tumour dissemination by re-infusing tumour cells into the circulation. Although IOCS has been extensively investigated in patients undergoing surgery for gynaecological, lung, urological, gastrointestinal, and hepatobiliary cancers, to date, there is no prior report of the use of IOCS in MSTS. We conducted a prospective observational study to evaluate whether LDF can eliminate tumour cells from blood salvaged during MSTS. Patients & Methods. After Institutional Review Board (IRB) approval, 21 consecutive patients with metastatic spinal tumours from a known epithelial primary (defined as originating from breast, prostate, thyroid, renal, colorectal, lung, nasopharyngeal) who were scheduled for MSTS were recruited with informed consent. During surgery, a IOCS device (Dideco, Sorin Group, Italy) was used to collect shed blood from the operative field. Salvaged blood was then passed through a leucocyte depletion filter (RS1VAE, Pall Corporation, UK). 15-ml specimens of blood were taken from each of three consecutive stages: (i) operative field prior to cell saver processing (Stage A); (ii) transfusion bag post-cell saver processing (Stage B); (iii) filtered blood after passage through LDF (Stage C). Cell blocks were prepared by the pathology department using a standardised laboratory protocol. From each cell block, 1 haematoxylin and eosin (H&E) slide, and 3 slides each labelled with one of the following monoclonal mouse cytokeratin antibodies AE1/3, MNF 116 and CAM 5.2 were prepared. The cytokeratin antibodies are highly sensitive and specific markers to identify tumour cells of epithelial origin. These slides were read by one of two consultant pathologists who were provided full access to information on operative notes, but were blinded to the actual stages from which the slides were derived. Results. One case was excluded when the final diagnosis was revised to infection instead of metastatic spine tumour. Of the remaining cases, 7/21 tested positive for tumour cells in Stage A, 2 positive in Stage B. No specimen tested positive for tumour cells in Stage C. In 5 cases, posterior instrumentation without tumour manipulation was performed. Discussion/Conclusion. In this first-ever study of cell saver use in spine tumour surgery, we prove that leucocyte-depletion filters (LDF) can effectively eliminate tumour cells from blood salvaged during MSTS. It is now possible to conduct a clinical trial to evaluate IOCS-LDF use in MSTS. Our results are consistent with published results of similar studies performed on IOCS and LDF use outside the field of orthopaedic surgery.
