Intraoperative localization in spinal surgery is essential to facilitate the best surgical outcome and to avoid wrong-site surgery. Intraoperative fluoroscopy is generally adequate, but anatomical variation, body habitus, and the inherent difficulties of fluoroscopy at certain levels may lead the surgeon astray. Here, the authors present their technique for preoperative localization that relies solely on fixed anatomical landmarks using CT-guided, percutaneously placed radiopaque markers. In the outpatient setting, low-dose CT scanning of the neuraxis is performed to identify fixed landmarks and, under local anesthesia and CT guidance, a pushable microcoil is inserted through a Chiba needle into the periosteum of the pedicle at the level of interest. The patient returns home with no precautions while the coil is in situ, and then the patient returns sometime later for surgery. Intraoperatively, typically a single lateral radiograph is required to visualize the coil and the level. Preoperative placement of radiopaque markers at the level of interest is an effective tool for avoiding wrong-site surgery, especially in circumstances in which fluoroscopy may be troublesome. The authors’ method is accurate, effective, and expeditious and can be performed easily in the outpatient setting.
Mendel Castle-Kirszbaum, Julian Maingard, Tony Goldschlager and Ronil V. Chandra
Mendel Castle-Kirszbaum, Scott Ayton and Tony Goldschlager
Tony Goldschlager, Roger Härtl, Jeffrey P. Greenfield, Vijay K. Anand and Theodore H. Schwartz
The gold-standard surgical approach to the odontoid is via the transoral route. This approach necessitates opening of the oropharynx and is associated with risks of infection, and swallowing and breathing complications. The endoscopic endonasal approach has the potential to reduce these complications as the oral cavity is avoided. There are fewer than 25 such cases reported to date. The authors present a consecutive, single-institution series of 9 patients who underwent the endonasal endoscopic approach to the odontoid.
The charts of 9 patients who underwent endonasal endoscopic surgery to the odontoid between January 2005 and August 2013 were reviewed. The clinical presentation, radiographic findings, surgical management, complications, and outcome, particularly with respect to time to extubation and feeding, were analyzed. Radiographic measurements of the distance between the back of the odontoid and the front of the cervicomedullary junction (CMJ) were calculated, as well as the location of any residual bone fragments.
There were 7 adult and 2 pediatric patients in this series. The mean age of the adults was 54.8 years; the pediatric patients were 7 and 14 years. There were 5 females and 4 males. The mean follow-up was 42.9 months. Symptoms were resolved or improved in all but 1 patient, who had concurrent polyneuropathy. The distance between the odontoid and CMJ increased by 2.34 ± 0.43 mm (p = 0.03). A small, clinically insignificant fragment remained after surgery, always on the left side, in 57% of patients. Mean times to extubation and oral feeding were on postoperative Days 0.3 and 1, respectively. There was one posterior cervical wound infection; there were 2 cases of epistaxis requiring repacking of the nose and no instances of breathing or swallowing complications or velopharyngeal insufficiency.
This series of 9 cases of endonasal endoscopic odontoidectomy highlights the advantages of the approach in permitting early extubation and early feeding and minimizing complications compared with transoral surgery. Special attention must be given to bone on the left side of the odontoid if the surgeon is standing on the right side.
Rodolfo Maduri, Daniele Starnoni and John Michael Duff
Tony Goldschlager, Nicolas Dea, Michael Boyd, Jeremy Reynolds, Shreyaskumar Patel, Laurence D. Rhines, Ehud Mendel, Marina Pacheco, Edwin Ramos, Tobias A. Mattei and Charles G. Fisher
Giant cell tumors (GCTs) of the spine are rare and complex to treat. They have a propensity for local recurrence and the potential to metastasize. Treatment is currently surgical and presents unique challenges due to the proximity of neural structures and the need for reconstruction. Denosumab has been shown in clinical trials to be an effective treatment for GCT, but has not yet been studied specifically in GCT of the spine or as a surgical adjunct. To the authors' knowledge this is the first such reported series.
A multicenter, prospective series of 5 patients with GCT of the spine treated with denosumab were included. Patient demographic data, oncological history, neurological status, tumor staging, treatment details and adverse events, surgical procedure, complications, radiological and histological responses, and patient outcome were analyzed.
All patients were women, with a mean age of 38 years, and presented with pain; 2 patients had additional neurological signs and symptoms. The mean duration of symptoms was 62 weeks. No patient had a prior tumor or metastatic disease at presentation. All patients had Enneking Stage III tumors and were treated with monthly cycles of 120 mg of denosumab, with initial additional loading doses on Days 8 and 15. Patients were given daily supplements of calcium (500 mg) and vitamin D (400 IU). There were no denosumab-related adverse events. All patients had a radiological response to denosumab. One patient failed to have a histological response to denosumab, with > 90% of tumor cells found to be viable on histological investigation.
This study reports the early experience of using denosumab in the treatment of spinal GCT. The results demonstrate a clinically beneficial radiological response and an impressive histological response in most but not all patients. Further experience with denosumab and longer patient follow-up is required. Denosumab has the potential to change the treatment paradigm for spinal GCT.
David Oehme, Peter Ghosh, Tony Goldschlager, Silviu Itescu, Susan Shimon, Jiehua Wu, Courtney McDonald, John M. Troupis, Jeffrey V. Rosenfeld and Graham Jenkin
Disc degeneration and associated low-back pain are major causes of suffering and disability. The authors examined the potential of mesenchymal precursor cells (MPCs), when formulated with pentosan polysulfate (PPS), to ameliorate disc degeneration in an ovine model.
Twenty-four sheep had annular incisions made at L2–3, L3–4, and L4–5 to induce degeneration. Twelve weeks after injury, the nucleus pulposus of a degenerated disc in each animal was injected with ProFreeze and PPS formulated with either a low dose (0.1 million MPCs) or a high dose (0.5 million MPCs) of cells. The 2 adjacent injured discs in each spine were either injected with PPS and ProFreeze (PPS control) or not injected (nil-injected control). The adjacent noninjured L1–2 and L5–6 discs served as noninjured control discs. Disc height indices (DHIs) were obtained at baseline, before injection, and at planned death. After necropsy, 24 weeks after injection, the spines were subjected to MRI and morphological, histological, and biochemical analyses.
Twelve weeks after the annular injury, all the injured discs exhibited a significant reduction in mean DHI (low-dose group 17.19%; high-dose group 18.01% [p < 0.01]). Twenty-four weeks after injections, the discs injected with the low-dose MPC+PPS formulation recovered disc height, and their mean DHI was significantly greater than the DHI of PPS- and nil-injected discs (p < 0.001). Although the mean Pfirrmann MRI disc degeneration score for the low-dose MPC+PPS–injected discs was lower than that for the nil- and PPS-injected discs, the differences were not significant. The disc morphology scores for the nil- and PPS-injected discs were significantly higher than the normal control disc scores (p < 0.005), whereas the low-dose MPC+PPS–injected disc scores were not significantly different from those of the normal controls. The mean glycosaminoglycan content of the nuclei pulposus of the low-dose MPC+PPS–injected discs was significantly higher than that of the PPS-injected controls (p < 0.05) but was not significantly different from the normal control disc glycosaminoglycan levels. Histopathology degeneration frequency scores for the low-dose MPC+PPS–injected discs were lower than those for the PPS- and Nil-injected discs. The corresponding high-dose MPC+PPS–injected discs failed to show significant improvements in any outcome measure relative to the controls.
Intradiscal injections of a formulation composed of 0.1 million MPCs combined with PPS resulted in positive effects in reducing the progression of disc degeneration in an ovine model, as assessed by improvements in DHI and morphological, biochemical, and histopathological scores.
Peter Ghosh, Robert Moore, Barrie Vernon-Roberts, Tony Goldschlager, Diane Pascoe, Andrew Zannettino, Stan Gronthos and Silviu Itescu
Chronic low-back pain of discal origin is linked strongly to disc degeneration. Current nonsurgical treatments are palliative and fail to restore the disc extracellular matrix. In this study the authors examined the capacity of ovine mesenchymal precursor cells (MPCs) to restore the extracellular matrix of degenerate discs in an ovine model.
Three adjacent lumbar discs of 24 adult male sheep were injected intradiscally with chondroitinase-ABC (cABC) to initiate disc degeneration. The remaining lumbar discs were used as normal controls. Three months after cABC injection, the L3–4 discs of all animals were injected with either a high dose (4 × 106 cells, in 12 sheep) or low dose (0.5 × 106 cells, in 12 sheep) of MPCs suspended in hyaluronic acid (HA). The adjacent L4–5 degenerate discs remained untreated; the L5–6 discs were injected with HA only. The animals were euthanized at 3 or 6 months after MPC injections (6 sheep from each group at each time point), and histological sections of the lumbar discs were prepared. Radiographs and MR images were obtained prior to cABC injection (baseline), 3 months after cABC injection (pretreatment), and just prior to necropsy (posttreatment).
Injection of cABC decreased the disc height index (DHI) of target discs by 45%–50%, confirming degeneration. Some recovery in DHI was observed 6 months after treatment in all cABC-injected discs, but the DHI increased to within baseline control values only in the MPC-injected discs. This improvement was accompanied by a reduction in MRI degeneration scores. The histopathology scores observed at 3 months posttreatment for the high-dose MPC–injected discs and at 6 months posttreatment for the low-dose MPC–injected discs were significantly different from those of the noninjected and HA-injected discs (p <0.001) but not from the control disc scores.
On the basis of the findings of this study, the authors conclude that the injection of MPCs into degenerate intervertebral discs can contribute to the regeneration of a new extracellular matrix.
Tony Goldschlager, Peter Ghosh, Andrew Zannettino, Stan Gronthos, Jeffrey V. Rosenfeld, Silviu Itescu and Graham Jenkin
There is an unmet need for a procedure that could generate a biological disc substitute while at the same time preserving the normal surgical practice of achieving anterior cervical decompression. The objective of the present study was to test the hypothesis that adult allogeneic mesenchymal progenitor cells (MPCs) formulated with a chondrogenic agent could synthesize a cartilaginous matrix when implanted into a biodegradable carrier and cage, and over time, might serve as a dynamic interbody spacer following anterior cervical discectomy (ACD).
Eighteen ewes were divided randomly into 3 groups of 6 animals. Each animal was subjected to C3–4 and C4–5 ACD followed by implantation of bioresorbable interbody cages and graft containment plates. The cage was packed with 1 of 3 implants. In Group A, the implant was Gelfoam sponge only. In Group B, the implant consisted of Gelfoam sponge with 1 million MPCs only. In Group C, the implant was Gelfoam sponge with 1 million MPCs formulated with the chondrogenic agent pentosan polysulfate (PPS). In each animal the cartilaginous endplates were retained intact at 1 level, and perforated in a standardized manner at the other level. Allogeneic ovine MPCs were derived from a single batch of immunoselected and culture-expanded MPCs isolated from bone marrow of outbred sheep (mixed stock). Radiological and histological measures were used to assess cartilage formation and the presence or absence of new bone formation.
The MPCs with or without PPS were safe and well-tolerated in the ovine cervical spine. There was no significant difference between groups in the radiographic or histological outcome measures, regardless of whether endplates were perforated or retained intact. According to CT scans obtained at 3 months after the operation, new bone formation within the interbody space was observed in the Gelfoam only group (Group A) in 9 (75%) of 12 interbody spaces, and 11 (92%) of 12 animals in the MPC cohort (Group B) had new bone formation within the interbody space. Significantly, in the MPC & PPS group (Group C), there were only 1 (8%) of 12 levels with new bone formation (p = 0.0009 vs Group A; p = 0.0001 vs Group B). According to histological results, there was significantly more cartilaginous tissue within the interbody cages of Group C (MPC & PPS) compared with both the control group (Group A; p = 0.003) and the MPC Group (p = 0.017).
This study demonstrated the feasibility of using MPCs in combination with PPS to produce cartilaginous tissue to replace the intervertebral disc following ACD. This biological approach may offer a means preserving spinal motion and offers an alternative to fusion to artificial prostheses.
David Oehme, Peter Ghosh, Susan Shimmon, Jiehua Wu, Courtney McDonald, John M. Troupis, Tony Goldschlager, Jeffrey V. Rosenfeld and Graham Jenkin
Following microdiscectomy, discs generally fail to undergo spontaneous regeneration and patients may experience chronic low-back pain and recurrent disc prolapse. In published studies, formulations of mesenchymal progenitor cells combined with pentosan polysulfate (MPCs+PPS) have been shown to regenerate disc tissue in animal models, suggesting that this approach may provide a useful adjunct to microdiscectomy. The goal of this preclinical laboratory study was to determine if the transplantation of MPCs+PPS, embedded in a gelatin/fibrin scaffold (SCAF), and transplanted into a defect created by microdiscectomy, could promote disc regeneration.
A standardized microdiscectomy procedure was performed in 18 ovine lumbar discs. The subsequent disc defects were randomized to receive either no treatment (NIL), SCAF only, or the MPC+PPS formulation added to SCAF (MPCs+PPS+SCAF). Necropsies were undertaken 6 months postoperatively and the spines analyzed radiologically (radiography and MRI), biochemically, and histologically.
No adverse events occurred throughout the duration of the study. The MPC+PPS+SCAF group had significantly less reduction in disc height compared with SCAF-only and NIL groups (p < 0.05 and p < 0.01, respectively). Magnetic resonance imaging Pfirrmann scores in the MPC+PPS+SCAF group were significantly lower than those in the SCAF group (p = 0.0213). The chaotropic solvent extractability of proteoglycans from the nucleus pulposus of MPC+PPS+SCAF-treated discs was significantly higher than that from the SCAF-only discs (p = 0.0312), and using gel exclusion chromatography, extracts from MPC+PPS+SCAF-treated discs also contained a higher percentage of proteoglycan aggregates than the extracts from both other groups. Analysis of the histological sections showed that 66% (p > 0.05) of the MPC+PPS+SCAF-treated discs exhibited less degeneration than the NIL or SCAF discs.
These findings demonstrate the capacity of MPCs in combination with PPS, when embedded in a gelatin sponge and sealed with fibrin glue in a microdiscectomy defect, to restore disc height, disc morphology, and nucleus pulposus proteoglycan content.
Charles G. Fisher, Tony Goldschlager, Stefano Boriani, Peter Paul Varga, Laurence D. Rhines, Michael G. Fehlings, Alessandro Luzzati, Mark B. Dekutoski, Jeremy J. Reynolds, Dean Chou, Sigurd H. Berven, Richard P. Williams, Nasir A. Quraishi, Chetan Bettegowda and Ziya L. Gokaslan
The National Institutes of Health recommends strategies to obtain evidence for the treatment of rare conditions such as primary tumors of the spine (PTSs). These tumors have a low incidence and are pathologically heterogeneous, and treatment approaches are diverse. Appropriate evidence-based care is imperative. Failure to follow validated oncological principles may lead to unnecessary mortality and profound morbidity. This paper outlines a scientific model that provides significant evidence guiding the treatment of PTSs.
A four-stage approach was used: 1) planning: data from large-volume centers were reviewed to provide insight; 2) recruitment: centers were enrolled and provided the necessary infrastructure; 3) retrospective stage: existing medical records were reviewed and completed with survival data; and 4) prospective stage: prospective data collection has been implemented. The AOSpine Knowledge Forum Tumor designed six modules: demographic, clinical, diagnostic, therapeutic, local recurrence, survival, and perioperative morbidity data fields and provided funding.
It took 18 months to implement Stages 1–3, while Stage 4 is ongoing. A total of 1495 tumor cases were captured and diagnosed as one of 18 PTS histotypes. In addition, a PTS biobank network has been created to link clinical data with tumor pathology and molecular analysis.
This scientific model has not only aggregated a large amount of PTS data, but has also established an international collaborative network of spine oncology centers. Access to large volumes of data will generate further research to guide and enhance PTS clinical management. This model could be applied to other rare neoplastic conditions. Clinical trial registration no.: NCT01643174 (ClinicalTrials.gov).