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Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_11 | Pages 313 - 313
1 Jul 2014
Tan J Lim J Chen Y Kumar N
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Summary. Neurological deficits resulting from spinal cord compression occur infrequently. When presented with neurological compromise, the most common management was radiotherapy, with surgery only being offered to patients who developed neurological deficit or pathological fracture resulting in unresolved severe pain post radiotherapy. Introduction. Nasopharyngeal carcinoma has been reported to have a higher incidence of distant metastases to the spine. This study was conducted to evaluate the incidence, presentation and management of neurological involvement related to spinal metastasis from nasopharyngeal carcinoma. Patients and Methods. 814 patients with the diagnosis of NPC who presented to the National University Hospital (NUH), Singapore, over a 5-year period (2007–2011) were recruited for this study. Case records from clinics, wards, operating theatres at NUH and nationwide electronic records of polyclinics and Emergency Medical Department (EMD) were obtained and reviewed. The data collected included demographics, medical history, radiologic and histopathology reports. Results. Of 814 patients with NPC, 99 had spinal metastasis. 26 were treated with radiotherapy, 25 with chemotherapy, 5 with both chemo and radiotherapy and 6 with surgery. Out of 6 patients requiring spinal surgical procedure, 3 had neurological deficits in the form of focal sensory or motor deficits and 4 had symptoms of pathologic fracture. One patient had both neurological deficit and pathological fracture. All these 6 patients were treated with a spinal surgical procedure of stabilization and/or decompression. Discussion/Conclusion. Spinal metastasis is common in patients with NPC and back pain is the usual presentation. Neurological deficits resulting from nerve root or spinal cord compression occur infrequently. When presented with neurological compromise, the most common management was radiotherapy, with surgery only being offered to patients who developed neurological deficit or pathological fracture resulting in unresolved severe pain post radiotherapy


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_1 | Pages 124 - 124
1 Jan 2017
Sakane M Tsukanishi T Funayama T Onishi S Ozeki E Hara I Yamazaki M
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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 spinal metastases in an emergency. The residual tumor may regrow and cause neurological deficits. We believe that ICG-lactosome-enhanced PDT can decrease the rate of local recurrence through reduction of the residual tumor. PDT with ICG-lactosome and NIR had an inhibitory effect on the growth of bone metastasis of a human breast cancer


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_11 | Pages 310 - 310
1 Jul 2014
Kumar N Chen Y Ahmed Q Lee V Wong H
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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. Spinal metastases originate from a myriad of primary cancers across various organ systems. If LDF can remove tumour cells from blood salvaged during surgery for spinal metastasis of different histological origin, then the finding can likely be extrapolated to several other fields of surgery where IOCS and LDF have not yet been attempted such as: neurosurgery, otolaryngology and general musculoskeletal oncology. Our results form a proof-of-concept for a paradigm shift in thinking regarding autotransfusion during spine tumour surgery


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_11 | Pages 309 - 309
1 Jul 2014
Chen Y Tai B Nayak D Kumar N Goy R Wong H
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Summary. Our meta-analysis showed that pooled mean blood loss during spinal tumour surgeries was 2180 ml. Standardised methods of calculating and reporting intra-operative blood loss are needed as it would be beneficial in the pre-operative planning of blood replenishment during surgery. Introduction. The vertebral column is the commonest site of bony metastasis, accounting for 18,000 new cases in North America yearly. Patients with spinal metastasis are often elderly, have compromised cardiovascular status, poor physiological reserve and altered immune status, all of which render them more susceptible to the complications of intra-operative blood loss and associated transfusion. Currently no consensus exists regarding the expected volume of blood lost during metastatic spine tumour surgery with various papers quoting anywhere between 1L to 6L. Knowledge of the expected blood loss prior to surgery however is important as it facilitates pre-operative planning, intra- and post-operative management of fluid balance and blood transfusion. We conducted a meta-analysis of published literature on spine tumour surgery to answer the question: “What is the expected blood loss in major spinal tumour surgery for metastatic spinal disease?”. Methods. A comprehensive online search of the English literature using Medline, Embase, and the Cochrane Central Register of Controlled Trials was performed. We included articles published from 31 January 1992 until 31 January 2012. This initial online search yielded 98 relevant articles. Two senior investigators independently reviewed all abstracts. The full text of articles that were deemed eligible for further consideration obtained and reviewed. Eighty five articles were excluded at this stage, largely due to lack of clear blood loss data, leaving 13 eligible articles. A hand search of the reference lists of relevant articles yielded 5 more articles. A total of 18 articles were included in the final meta-analysis of blood loss data. Disagreements regarding eligibility of articles for analysis were resolved by consensus. Selected articles for final analysis were independently graded according to the Centre for Evidence-Based Medicine (CEBM) Levels of Evidence. We evaluated the possibility of publication bias by obtaining a funnel plot (created by plotting the sample size against the effect estimate). The Egger's regression asymmetry test was used to assess the existence of publication bias. Results. Eighteen selected articles had a total of 785 patients who had undergone major spine tumour surgery for metastatic spinal disorders. The pooled estimate of the blood loss occurring during spinal tumour surgeries was calculated to be 2180ml (95%CI: 1805–2554ml). Apart from two studies which reported significant mean blood loss of more than 5500 ml, the resulting funnel plot suggested absence of publication bias. This was confirmed by Egger's test which did not show any small-study effects (p=0.119). However, there was strong evidence of heterogeneity between studies with I2=90% (p<0.001). Conclusions. The expected blood loss of a patient undergoing major surgery for spinal tumour constitutes more than a third of the circulating blood volume in a typical cancer patient with significantly impaired physiological reserve. Moreover, cases of catastrophic blood loss exceeding 5L exist in almost every series evaluated in this paper, with some reaching as much as 17–18L. Blood loss is a significant problem during spine tumour surgery and concerted effort is needed to address it