There is a paucity of published Canadian literature comparing lumbar total disc arthroplasty (LDA) to fusion on patient outcomes in degenerative spondylosis. The purpose of this study is to quantify and compare the long-term patient reported outcomes following LDA and matched-fusion procedures. We conducted a matched-cohort study comparing consecutive patients enrolled by CSORN who underwent standalone primary LDA or hybrid techniques for degenerative disk disease between 2015–2019. Fusion patients were included by a primary diagnosis of degenerative disk disease, chief complaint of back pain, who received a primary fusion irrespective of technique. Fusion patients were matched by number of involved levels of surgery to LDA counterparts. Outcome scores and patient satisfaction were assessed preoperatively and 2-years postoperatively. 97 patients (39-female, 58-male) underwent LDA or hybrid construct up to 4 levels. 94 patients (52-female, 42-male) underwent a lumbar fusion were selected based on inclusion criteria. 36 LDA and 57 Fusion patients underwent a 1-level surgery. 39 LDA and 25 Fusion patients underwent 2-level surgery. 18 LDA and 7 Fusion patients underwent 3-level surgery. 4 LDA and 5 Fusion patients underwent a 4-level procedure. Slight differences in average cohort age were found (LDA-43.4yrs, Fusion-49.8yrs, p<0.01). Cohort preoperative-BMI (LDA-27.0kg/m2, Fusion-27.9kg/m2, p=0.29) and total comorbidities (LDA-2.6, Fusion-2.1, p=0.05) demonstrated no clinically significant differences. At 2 year follow-up, no differences were found in ODI improvement (LDA-20.32pts, Fusion-17.02pts, p=0.36), numerical back-pain improvement (LDA-3.5pts, Fusion-3.06pts, p=0.40), numerical leg-pain improvement (LDA-1.67pts, Fusion-1.87pts, p=0.76), and Health Scale improvement (LDA-17.12, Fusion-10.73, p=0.20) between cohorts. Similar positive findings were found in subgroups stratified by number of surgical levels. Satisfaction rate at 2 years was 86.7% and 82.4% for LDA and Fusion patients respectively. There didn't appear to be significant differences in outcomes or satisfaction through 2 years comparing patients who underwent LDA (whether used in isolation or as part of a hybrid construct) for debilitating degenerative disk disease and isolated spinal fusion for back dominant pain.
A novel bipolar cooled radiofrequency ablation probe, optimised for bone metastases applications, is shown in two preclinical models to offer a safe and minimally invasive treatment option that can ablate large tissue volumes and preserve the regenerative ability of bone. Use of radiofrequency ablation (RFA) in treating of skeletal metastases has been rising, yet its impact on bone tissue is poorly understood. 2–11 RF treatment induces frictional heating and effectively necrotises tissue in a local and minimally invasive manner.1 Bipolar cooled RF (BCRF) is a significant improvement to conventional RF whereby larger regions can be safely treated, protecting sensitive neighbouring tissues from thermal effects. This study aimed to evaluate the safety and feasibility of a novel bipolar RFA probe to create large contained lesions within healthy pig vertebrae and its determine its effects on bone and tumour cells in a rabbit long bone tumour model.Summary
Introduction
Maintenance of vertebral mechanical stability is of paramount importance to prevent pathologic fractures and resultant neurologic compromise in individuals with spinal metastases. Current non-surgical treatments for vertebral metastases (i.e. chemotherapy, bisphophonates (BP) and radiation) yield variable responses in the tumour and surrounding bone. Photodynamic therapy (PDT) is a novel, minimally-invasive technology that utilizes a drug activated by light at a specific non-thermal wavelength to locally destroy tumour cells. Previously, we observed that PDT can ablate cancer cells within bone and yield short-term (1-week) improvements in vertebral architecture and biomechanical strength, particularly when combined with BP therapy. This study aims to evaluate the effects of PDT in vertebral bone over a longer (6-week) time period, alone and combined with previous BP treatment, to determine if improvements in skeletal architecture and strength are maintained. Fourty healthy rnu/rnu rats were randomly assigned to four treatment groups: (i) untreated control, (ii) BP only, (iii) PDT only and (iv) PDT following BP. BP treatments were administered on day 0 via subcutaneous injection of zoledronic acid. PDT was administered on day 7 via an intravenous injection of BPD-MA photosensitizer. A flat-cut optical fiber was inserted percutaneously adjacent to lumbar vertebra L2. After a 15-minute drug-light interval, 75J of light energy was delivered from a 690nm laser. Six weeks later, animals were euthanized. Structural properties of excised L2 vertebral bodies were quantified through semi-automated analysis of micro-CT images. In of the specimens, mechanical properties were evaluated by loading the L2 vertebral body to failure in axial compression. The remaining L2 vertebrae were analyzed for morphology, osteoid formation and osteoclast activity using histological methods.Purpose
Method
Versican is a member of the large aggregating chondroitin sulfate proteoglycan family. Structurally, it is made up of an N-terminal G1 domain, a glycosamingoglycan attachment region, and a C-terminus containing a selectin-like (G3) domain. Versican is highly expressed in the interstitial tissues at the invasive margins of breast carcinoma and predictive of relapse and overall survival. The purpose of the study to investigate the role of of versican G3 domain in breast cancer bone metastasis. Mouse mammary tumor cell lines 66c14, 4T07 and 4T1, and human breast cancer cell lines MT-1, MDA-MB-468 and MDA-MB-231 were stably transfected with versican G3. Effects of expression of versican G3 on cell proliferation, migration, invasion, cell cycle progression, and EGFR signaling were observed. The effects of G3 on cell viability in the conditional media of serum free, apoptotic agent C2-ceramide, and chemotherapeutic agents, including Docetaxel, Doxorubicin, Epirubicin were investigated. Colony formation assay and mammosphere formation assay were performed. A syngeneic orthotopic animal model was used to do the in vivo study.Purpose
Method
Nucleus pulposus (NP) replacements represent a less invasive alternative for treatment of early stage degenerative disc disease (DDD). Hydrogel based NP replacements are of particular interest as they can be injected/implanted using minimally invasive surgical (MIS) techniques to re-establish mechanical integrity and as a scaffold for regeneration. A thiol-modified hyaluronan elastin-like polypeptide (TMHA/EP) hydrogel crosslinked using polyethylene diacrylate has shown promise as a potential NP replacement for DDD in vitro. This study aims to assess the mechanical properties of this hydrogel when injected into an induced early stage DDD porcine model and to determine the optimal injection method for delivery. It is hypothesized that minimally invasive injection of the TMHA/EP material can restore mechanical behaviour of spinal motion segments in early stage DDD. Intervertebral disc (IVD) degeneration was enzymatically induced in L2-L3 and L4-L5 lumbar levels in 10 Yorkshire boars using chondroitinase ABC (n=20 discs). An additional three animals served as healthy controls (n=6 discs). Following a four-week degradation period, the TMHA/EP solution (250microL in a 3:1 weight ratio) was injected into the degenerate NP of 16 discs by one of two MIS techniques: A direct 18G needle injection or a modified kyphoplasty technique (MKT) in which a balloon angiocatheter was inserted through an 11G trocar into the IVD and inflated to create a cavitary defect that was then filled with the hydrogel. Excised motion segments were tested in axial compression under a load of 400N and in axial rotation (AR), lateral bending (LB) and flexion/extension (FE) at 5Nm. Range of motion (ROM), neutral zone (NZ) length, NZ stiffness (NZStiff) and axial compressive stiffness (ACStiff) were quantified.Purpose
Method
Rodents are often used as preclinical models for investigating the biomechanical consequences of spinal pathologies and interventions. Growth plates are present within rat vertebrae throughout life and may alter the vertebral biomechanics. This study investigates the biomechanical response of rat-tail vertebrae to axial compressive loading using μCT imaging and image registration to spatially resolve strain fields. The sixth caudal vertebrae of eight immunocompromised (rnu/rnu) rats were μCT scanned (17.5 ×17.5×17.5μm/pixel) in both loaded (27N-32N axial compression) and unloaded configurations. Image registration was used to calculate strain and displacement fields in the bone due to the applied load by finding a spatial mapping between the two scans. Strain was resolved to varying spatial resolutions; high strain gradient regions, such as the growth plates, were analyzed to higher spatial resolutions. Axial strains calculated by image registration ranged from 2% in tension to 16% in compression with an average axial strain of 1.6% in compression. In seven rats the majority of the strain measured within the vertebrae was concentrated in the growth plate. Very soft growth plates in three specimens resulted in maximum axial strains from 10–16% in compression. The remaining four rats with strain concentrations in the growth plate had maximum axial strains ranging from 2.2%–3.2%. Centrally located strain concentrations of lower magnitudes and more limited spatial extent were observed in the trabecular bone. The majority of the strain within the rat vertebrae was absorbed by the growth plates. The amount of strain within the growth plate is important to consider when interpreting biomechanical data on rat vertebrae. Load application to rodent vertebrae will first compress the growth plate and only following compression of this structure cause significant development of displacement and strains within the trabecular and cortical bone. This insight into the biomechanical response of rat vertebrae is apparent through the application of image registration to analyse vertebral body behaviour; such information would not be evident in analysing preclinical whole vertebral body response using finite element modeling or experimental testing protocols.
To evaluate the effect of wait time to surgery on patient derived generic and disease-specific functional outcome following lumbar surgery. Study cohort of seventy patients undergoing elective posterior lumbar spinal surgery for degenerative conditions. Prospectively collected SF-36 and Oswestry Disability questionnaires administered preoperatively, six weeks, six months, one year postoperatively. Time intervals from onset of symptoms to initial consultation by family physician through investigations, spinal surgical consultation and time spent on the surgical waiting list to surgery quantified. Time intervals compared to patient-specific improvements in reported outcome following surgery using Cox-Regression analysis. The effect of patient and surgical parameters on wait time was evaluated using median time as a reference for patients with either a longer or shorter wait. Patient follow-up completed in fifty-three (76%). Improvements in patient derived outcome were observed comparing post-operative to pre-operative baseline scores (p<
0.05). The greatest improvements were observed in aspects relating to physical function and pain. A longer wait to surgery was associated with less improvement in surgical outcome (p<
0.05, SF-36 domains BP, GH, RP, VT, and Physical Component Scores). The greatest impact observed was a prolonged surgical wait-list time on SF-36 PCS scores following surgery (Hazard’s ratio 3.53). Patients requiring spinal fusion had a longer wait when compared to those not requiring fusion (p<
0.05). A longer wait time to spinal surgery can negatively influence surgical results as quantified by patient derived functional outcome measures. Surgery resulted in the greatest improvement in pain severity and physical aspects of function, however, these areas also appeared the most impacted by a longer wait to surgery.
A predictive model for final kyphosis was tested by evaluating the radiographs of forty-three patients with traumatic burst fractures. Since clinical outcomes are related to final kyphosis in the ambulatory patient rather than on the initial supine injury radiograph, the ability to predict final kyphosis is beneficial in determining treatment. This study demonstrated that in the appropriately selected patient for conservative care, the limit of final-kyphosis(Kf) can be predicted from the intial-kyphosis(KI) , such that Kf= <
KI+.5KI . Outliers from this equation were patients who had unrecognized posterior column fractures, superior and inferior end-plate fractures, and/or multiple level of injury. The purpose of this study was to define a prediction model that afforded clinicians the ability to define final kyphosis from initial supine films in order to guide the management of stable burst fractures. This study has demonstrated that as a rule of thumb, the final absolute kyphosis for stable burst fractures can be expected to be up to Ki (initial absolute kyphosis) + 1.5Ki. Outliers were found to be fractures with unrecognized posterior element injury, both superior and inferior endplate fractures and multiple level injuries. The final kyphosis is clinically more relevant than the initial kyphosis in terms of functional outcome after conservative management. A prediction model for final kyphosis based on initial injury films can help guide the clinician for optimal management. Retrospective radiographic analysis was performed on forty-three patients with a minimum follow up six months. All patients suffered traumatic burst fractures, which were deemed stable as to be satisfactorily managed in a brace. Serial radiographs were used to determine initial (Ki) and final (Kf), Kyphosis angles. Predicted Kf was determined using the equation Kf =Ki + 1.5 Ki. The initial absolute kyphosis was the measured kyphosis using the Cobb technique and including the loss of the expected normal lordosis of that spinal segment. Inclusion criteria included burst fractures at between levels T10 – L3 in the neurologically intact patient. The equation accurately predicted the final outcome , Kf, in 70 % of the cases. In 20% of the cases, the Kf was less than expected. (Acceptable clinical result). In 10% of the cases, Kf was greater than predicted or achieved a clinically unacceptable kyphotic angulation requiring secondary surgery. In this group of outliers, post-hoc analysis identified unrecognized posterior element injury, both superior and inferior endplate fractures and multiple level injuries. In traumatic burst fractures, the goal of management is to protect the spine during healing while maintaining an acceptable alignment, which will not lead to late pain and deformity. A final absolute kyphosis angle, Kf, from twenty to thirty degrees has been variably regarded as a threshold to obtain a good clinical outcome. Criteria for stability have been previously documented, however variables are based on initial presentation. Aside from careful classification of the fracture type, the current “rule of thumb” prediction model for Kf may further help the clinician with management decisions.
Photodynamic therapy is a promising cancer treatment that employs wavelength-specific light in combination with a photosensitizing agent to induce local tumor destruction by photochemical generation of cytotoxic singlet oxygen. Clinical PDT has been evaluated for a variety of primary tumors, however, its use in spinal metastases to our knowledge has not been previously evaluated. A practical consideration is the ability to deliver light to bone. The investigators are evaluating a novel method of applying light to targeted spinal lesions using a minimally invasive technique similar to percutaneous vertebroplasty. This preliminary preclinical study evaluates the feasibility and efficacy of spinal PDT. To evaluate the feasibility and efficacy of spinal meta-static photodynamic therapy (PDT) using a percutaneous minimally invasive surgical approach similar to that of vertebroplasty in a preclinical model of bone metastases. A bioluminescent metastatic model was developed (intracardiac injection 2x106 MT-1Luc human breast cancer cells; Spinal PDT caused a reduction in bioluminescence of targeted lesions (66% to 87% in three hour drug-light group using light fluence rates of 25J and 150J, respectively; p<
0.05). The most selective drug-light interval was twenty-four hours where PDT induced tumor cell apoptosis/necrosis occurred, however, no spinal cord injury was observed. The greatest anti-tumor effect was observed at the three hour drug-light interval but observations of neurologic sequalae (9/22 animals) highlight the importance of ongoing study to closely define the therapeutic window of PDT. Drug dosimetry and the drug-light interval are critical in establishing an efficacious and safe treatment range for spinal PDT. Bioluminescent reporter imaging provides an
Photodynamic therapy (PDT) is a promising new treatment for spinal metastases; however, the effects of PDT on bone are largely unknown. This study assessed the impact of PDT on spinal stability in rats at high (non-therapeutic) drug and LASER light doses. Spinal stability was assessed using stereological measures attained from in vitro μCT scans. High doses of PDT were shown to cause a reduction in vertebral density. Postoperative paralysis was also noted in a subset of animals treated. Tumour-involved vertebrae are already mechanically weakened; as such it is essential to establish a safe and efficacious therapeutic window for vertebral PDT. This study assessed the effect of high doses of photodynamic therapy (PDT) on biomechanical stability and bone density of lumbar vertebrae. PDT can cause damage to the vertebral bone and induce paralysis when treatment is applied at very high doses in the rat spine. PDT is a promising new treatment for spinal metastases however, it is important to understand its effect on vertebral bone in order to closely define the therapeutic window for safety and efficacy. Trabecular bone density decreased from L1–L3 in normal, untreated rats. The L2 vertebra when treated with high dose PDT was shown to have decreased bone density as compared to both L1 and L3. As expected, tumour-bearing rats had lower vertebral densities than normals. Rnu/Rnu rats were separated into normal controls, normals treated with PDT and tumour-bearing rats. Rats treated with PDT received an intercardiac injection of 2.5mg/Kg BPD-MA. The drug was activated through administration of 500J (300mA) of a non-thermal 690nm LASER adjacent to the L2 vertebral body. After one week, in vitro μCT scans were taken of L1–L3 and stereological quantities measured. The demonstrated reduction of bone density as quantified one week following treatment is important when considering spinal stability in the potential use of PDT to treat vertebral metastases. We have observed that the therapy can induce paralysis when treatment is applied at high doses in the rat spine. The intermediate and long-term effects of PDT on bone remain unknown and require ongoing study.
There is increasing knowledge regarding the functional outcome of patients following posterior lumbar spinal surgery for degenerative conditions of the spine. There is less known regarding the expectations patients have for spinal surgery and how that may relate to commonly reported surgical outcome measures. It was the purpose of this study to evaluate the results of elective lumbar spinal surgery as it relates to patient expectations for outcome. and outcome as quantified by both physician reported outcome and patient derived generic and disease-specific measures. Patient expectations for surgery were evaluated in one hundred and fifty-five consecutive patients undergoing posterior lumbar surgery for degenerative conditions (single institution, two surgeons). SF-36+Oswestry disability was quantified preoperatively, and serially postoperatively. Preoperative expectations (pain relief, sleep, recreational, ADL, work return) were documented and postoperative expectations quantified at time of anticipated maximal medical improvement (6mos decompressions,1yr with fusions). Mean preoperative SF-36 MCS and PCS scores were 3.4 and 1.2 S.D. below age/gender matched Canadian norms. Although patients reported improvements in SF-36+Oswestry scores following surgery, mean SF-36 MCS and PCS scores were still 2 and 1.5 S.D. below norms. Mean Oswestry disability improved from 48.7%±1.7% to 23.1±1.9%. Expectations for surgery were met in 81%(responders:143/155). Of 19%(27/143) where expectations were not met, 6/27 have either nonunion, technical, or medical factors. There was no difference in mean age, gender, comorbidity, procedure type and follow-up comparing patients where expectations were met to those that were not. Patients where expectations were not met reported lower preoperative SF-36 (GH and VT) domain scores (p=0.02 and 0.04, respectively), however, preoperative Oswestry, SF-36 MCS and PCS scores were not significantly different. Patients were less satisfied if they had prior lumbar surgery (p=0.02) or involved in WCB/litigation (p<
0.001). We note 15%(21/143) where expectations were not met and there were no apparent surgical or medical confounds to account. There are likely other factors that may influence patient perception and expectation for treatment which requires further study.