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Von Hippel-Lindau (VHL) disease is a tumor predisposition syndrome caused by mutations in the VHL gene that presents with visceral neoplasms and growths, including clear cell renal cell carcinoma, and central nervous system manifestations, such as hemangioblastomas of the brain and spine. The pathophysiology involves dysregulation of oxygen sensing caused by the inability to degrade HIFα, leading to the overactivation of hypoxic pathways. Hemangioblastomas are the most common tumors in patients with VHL and cause significant morbidity. Until recently, there were no systemic therapies available for patients that could effectively reduce the size of these lesions. Belzutifan, the first approved HIF-2α inhibitor, has demonstrated benefit in VHL-associated tumors, with a 30% response rate in hemangioblastomas and ~30%–50% reduction in their sizes over the course of treatment. Anemia is the most prominent adverse effect, affecting 76%–90% of participants and sometimes requiring dose reduction or transfusion. Other significant adverse events include hypoxia and fatigue. Overall, belzutifan is well tolerated; however, long-term data on dosing regimens, safety, and fertility are not yet available. Belzutifan holds promise for the treatment of neurological manifestations of VHL and its utility may influence the clinical management paradigms for this patient population.

Study design This was a cross-sectional study. Objective The objective of this study is to report the impact of COVID-19 on spine surgery fellow education and readiness for practice. Summary of background data COVID-19 has emerged as one of the most devastating global health crises of our time. To minimize transmission risk and to ensure availability of health resources, many hospitals have cancelled elective surgeries. There may be unintended consequences of this decision on the education and preparedness of current surgical trainees. Materials and methods A multidimensional survey was created and distributed to all current AO Spine fellows and fellowship directors across the United States and Canada. Results Forty-five spine surgery fellows and 25 fellowship directors completed the survey. 62.2% of fellows reported >50% decrease in overall case volume since cancellation of elective surgeries. Mean hours worked per week decreased by 56.2%. Fellows reported completing a mean of 188.4±64.8 cases before the COVID-19 crisis and 84.1% expect at least an 11%-25% reduction in case volume compared with previous spine fellows. In all, 95.5% of fellows did not expect COVID-19 to impact their ability to complete fellowship. Only 2 directors were concerned about their fellows successfully completing fellowship; however, 32% of directors reported hearing concerns regarding preparedness from their fellows and 25% of fellows were concerned about job opportunities. Conclusions COVID-19 has universally impacted work hours and case volume for spine surgery fellows set to complete fellowship in the middle of 2020. Nevertheless, spine surgery fellows generally feel ready to enter practice and are supported by the confidence of their fellowship directors. The survey highlights a number of opportunities for improvement and innovation in the future training of spine surgeons. Level of evidence Level III.

Spinal oncology has had many advancements often necessitating serial imaging for post-surgical treatment planning and close follow up. Traditional spinal instrumentation introduces artifact into MRI and CT imaging, which can reduce the efficacy of follow up imaging and treatment. Newly created carbon-fiber instrumentation can offer many advantages compared to traditional instrumentation while typically maintaining biomechanical stability. The utility of this new instrumentation continues to evolve as more surgeons utilize these materials, which can improve patient outcomes. We illustrate the utility of this new hardware technology through various patient examples., Carbon fiber, Oncology, Radiation, Reconstruction.

Intramedullary spinal cord tumors (IMSCTs) are rare neoplasms that have limited treatment options and are associated with high rates of morbidity and mortality. To better understand the genetic basis of these tumors we performed whole exome sequencing on 45 tumors and matched germline DNA, including twenty-nine spinal cord ependymomas and sixteen astrocytomas. Though recurrent somatic mutations in IMSCTs were rare, we identified NF2 mutations in 15.7% of tumors (ependymoma, N = 7; astrocytoma, N = 1), RP1 mutations in 5.9% of tumors (ependymoma, N = 3), and ESX1 mutations in 5.9% of tumors (ependymoma, N = 3). We further identified copy number amplifications in CTU1 in 25% of myxopapillary ependymomas. Given the paucity of somatic driver mutations, we further performed whole-genome sequencing of 12 tumors (ependymoma, N = 9; astrocytoma, N = 3). Overall, we observed that IMSCTs with intracranial histologic counterparts (e.g. glioblastoma) did not harbor the canonical mutations associated with their intracranial counterparts. Our findings suggest that the origin of IMSCTs may be distinct from tumors arising within other compartments of the central nervous system and provides the framework to begin more biologically based therapeutic strategies.

Background Spinal chordomas, a subtype of primary spinal column malignancies (PSCM), are rare tumors with poor prognosis, and we have limited understanding of the molecular drivers of neoplasia. Methods Study design was a retrospective review of prospectively collected data with cross-sectional survival. Archived paraffin embedded pathologic specimens were collected for 133 patients from 6 centers within Europe and North America between 1987 and 2012. Tumor DNA was extracted and the human telomerase reverse transcriptase (hTERT) promoter was sequenced. The hTERT mutational status was correlated with overall survival (OS) and time to first local recurrence. Results Ninety-two chordomas, 26 chondrosarcomas, 7 osteosarcomas, 3 Ewing’s sarcomas, and 5 other malignant spinal tumors were analyzed. Median OS following surgery was 5.8 years (95% CI: 4.6 to 6.9) and median time to first local recurrence was 3.9 years (95% CI: 2.5 to 6.7). Eight chordomas, 2 chondrosarcomas, 1 Ewing’s sarcoma, and 1 other malignant spinal tumor harbored either a C228T or C250T mutation in the hTERT promoter. In the overall cohort, all patients with hTERT mutation were alive at 10 years postoperative with a median OS of 5.1 years (95% CI: 4.5 to 6.6) (P = 0.03). hTERT promoter mutation was observed in 8.7% of spinal chordomas, and 100% of chordoma patients harboring the mutation were alive at 10 years postoperative compared with 67% patients without the mutation (P = 0.05). Conclusions We report for the first time that hTERT promoter mutations C228T and C250T are present in approximately 8.7% of spinal chordomas. The presence of hTERT mutations conferred a survival benefit and could potentially be a valuable positive prognostic molecular marker in spinal chordomas.

Background Chordomas are the most common primary spinal column malignancy in the United States. The aim of this study was to determine whether chordomas may be detected by evaluating mutations in circulating tumor DNA (ctDNA). Methods Thirty-two patients with a biopsy-confirmed diagnosis of chordoma had blood drawn pre-operatively and/or at follow-up appointments. Mutations in the primary tumor were identified by whole exome sequencing and liquid biopsy by ddPCR and/or RACE-Seq was used to detect one or more of these mutations in plasma ctDNA at concurrent or later time points. Results At the time of initial blood draw, 87.1% of patients were ctDNA positive (P Conclusions Detection of ctDNA mutations may allow for the detection and monitoring of disease progression for chordomas.

OBJECTIVEResection of metastatic spine tumors can improve patients’ quality of life by addressing pain or neurological compromise. However, resections are often complicated by wound dehiscence, infection, instrumentation failures, and the need for reoperation. Moreover, when reoperations are needed, the most common indication is surgical site infection and wound breakdown. In turn, wound reoperations increase morbidity as well as the length and cost of hospitalization. The aim of this study was to examine perioperative risk factors associated with increased rate of wound reoperations after metastatic spine tumor resection.METHODSA retrospective study of patients at a single institution who underwent metastatic spine tumor resection between 2003 and 2013 was conducted. Factors with a p value < 0.200 in a univariate analysis were included in the multivariate model.RESULTSA total of 159 patients were included in this study. Karnofsky Performance Scale score > 70, smoking status, hypertension, thromboembolic events, hyperlipidemia, increasing number of vertebral levels, and posterior approach were included in the multivariate analysis. Thromboembolic events (95% CI 1.19–48.5, p = 0.032) and number of levels involved were independently associated with increased wound reoperation rates in the multivariate model. For each additional spinal level involved, the risk for wound reoperations increased by 21% (95% CI 1.03–1.43, p = 0.018).CONCLUSIONSAlthough wound complications and subsequent reoperations are potential risks for all patients with metastatic spine tumor, due to adjuvant radiotherapy and other medical comorbidities, this study identified patients with thromboembolic events or those requiring a larger incision as being at the highest risk. Measures intended to decrease the occurrence of perioperative venous thromboembolism and to improve wound care, especially for long incisions, may decrease wound-related revision surgeries in this vulnerable group of patients.

Background Robotic-assisted techniques have been implemented in the surgical treatment of tumors in the pelvis, abdomen, and thorax. In pelvic tumors, robotic-assisted techniques evade the need for sizable surgical exposure, but make stimulation of the nerves of the sacral plexus very difficult. Objective To describe how laparoscopic robotic-assisted surgery can couple with tools such as the nerve stimulator to aid in the resection of presacral masses emanating from the neural elements and potentially improve neurological outcome by preventing inadvertent injury to involved nerves. Methods A patient with a large presacral ganglioneuroma underwent resection using the DaVinci system (Intuitive Surgical, Sunnyvale, California) for robotic assistance. A nerve stimulator was coupled to the bipolar cautery instrument of the DaVinci robot to define the presence of functional nerves in the surroundings of the tumor. Results By coupling a nerve stimulator to the bipolar cautery instrument of the DaVinci robot (Intuitive Surgical), it was possible to identify important neural structures in close proximity to the tumor. After identifying functional nerves, the surgeon was able to preserve them and preserve neurological function avoiding motor dysfunction. Conclusion The use of a nerve stimulator coupled to the bipolar cautery instrument of the DaVinci robot (Intuitive Surgical) during laparoscopic, robotic-assisted surgery for resection of presacral masses is safe and feasible. In addition to the preoperative evaluation, intraoperative monitoring and stimulation of nerves in close proximity to the tumor and also exiting through neural foramina involved by the tumor allowed the surgeon to understand the anatomy and preserve neurological function while obtaining optimal surgical resection.

Background Surgical treatment of severe cervicothoracic kyphotic deformity may require the use of 3-column osteotomies such as the pedicle subtraction osteotomy and vertebral column resection (VCR), or VCR with anterior longitudinal ligament resection. Such procedures are extensive and are associated with high intra- and perioperative morbidity, in part, due to the need for risky reduction maneuvers. Objective To describe a novel technique utilizing a laterally placed articulating hinge to facilitate kyphotic deformity correction of the cervicothoracic spine. Methods A patient with severe chin-on-chest deformity of the cervicothoracic spine presented for evaluation and a 2-stage VCR with anterior longitudinal ligament resection was planned. To reduce the risk of intraoperative neurological injury and for increased control during reduction maneuvers, lateral instrumentation was placed through the chest wall resection above and below the level of VCR, which was adjoined with an articulating hinge rod apparatus. Results Satisfactory reduction of the kyphosis was achieved utilizing the hinge rod apparatus for controlled deformity correction. The patient remained neurologically intact following this procedure with improvement in their spinal alignment. Conclusion We present a novel technique utilizing a lateral hinge rod apparatus for efficient, controlled correction of severe kyphotic deformity.

BACKGROUND AND PURPOSE: The early diagnosis of spinal vascular malformations suffers from the nonspecificity of their clinical and radiologic presentations. Spinal angiography requires a methodical approach to offer a high diagnostic yield. The prospect of false-negative studies is particularly distressing when addressing conditions with a narrow therapeutic window. The purpose of this study was to identify factors leading to missed findings or inadequate studies in patients with spinal vascular malformations. MATERIALS AND METHODS: The clinical records, laboratory findings, and imaging features of 18 patients with spinal arteriovenous fistulas and at least 1 prior angiogram read as normal were reviewed. The clinical status was evaluated before and after treatment by using the Aminoff-Logue Disability Scale. RESULTS: Eighteen patients with 19 lesions underwent a total of 30 negative spinal angiograms. The lesions included 9 epidural arteriovenous fistulas, 8 dural arteriovenous fistulas, and 2 perimedullary arteriovenous fistulas. Seventeen patients underwent endovascular (11) or surgical (6) treatment, with a delay ranging between 1 week and 32 months; the Aminoff-Logue score improved in 13 (76.5%). The following factors were identified as the causes of the inadequate results: 1) lesion angiographically documented but not identified (55.6%); 2) region of interest not documented (29.6%); or 3) level investigated but injection technically inadequate (14.8%). CONCLUSIONS: All the angiograms falsely reported as normal were caused by correctible, operator-dependent factors. The nonrecognition of documented lesions was the most common cause of error. The potential for false-negative studies should be reduced by the adoption of rigorous technical and training standards and by second opinion reviews.

OBJECTIVE The aim of this study was to investigate the incidence of spinal tuberculosis (TB) in the US between 2002 and 2011. METHODS The Nationwide Inpatient Sample database from 2002 to 2011 was used to identify patients with a discharge diagnosis of TB and spinal TB. Demographic and hospital data were obtained for all admissions, and included age, sex, race, comorbid conditions, insurance status, hospital location, hospital teaching status, and hospital region. The incidence rate of spinal TB adjusted for population growth was calculated after application of discharge weights. RESULTS A total of 75,858 patients with a diagnosis of TB were identified, of whom 2789 had a diagnosis of spinal TB (3.7%); this represents an average of 278.9 cases per year between 2002 and 2011. The incidence of spinal TB decreased significantly—from 0.07 cases per 100,000 persons in 2002 to 0.05 cases per 100,000 in 2011 (p < 0.001), corresponding to 1 case per 2 million persons in the latter year. The median age for patients with spinal TB was 51 years, and 61% were male; 11.6% were patients with diabetes, 11.4% reported recent weight loss, and 8.1% presented with paralysis. There were 619 patients who underwent spinal surgery for TB, with the most common location being the thoracolumbar spine (61.9% of cases); 50% of patients had instrumentation of 3 or more spinal segments. CONCLUSIONS During the examined 10-year period, the incidence of spinal TB was found to significantly decrease over time in the US, reaching a rate of 1 case per 2 million persons in 2011. However, the absolute reduction was relatively small, suggesting that although it is uncommon, spinal TB remains a public health concern and most commonly affects male patients approximately 50 years of age. Approximately 20% of patients with spinal TB underwent surgery, most commonly in the thoracolumbar spine.

Spinal screw placement is a challenging task due to small bone corridors and high risk of neurological or vascular complications, benefiting from precision guidance/navigation and quality assurance (QA). Implicit to both guidance and QA is the definition of a surgical plan-i.e. the desired trajectories and device selection for target vertebrae-conventionally requiring time-consuming manual annotations by a skilled surgeon. We propose automation of such planning by deriving the pedicle trajectory and device selection from a patient's preoperative CT or MRI. An atlas of vertebrae surfaces was created to provide the underlying basis for automatic planning-in this work, comprising 40 exemplary vertebrae at three levels of the spine (T7, T8, and L3). The atlas was enriched with ideal trajectory annotations for 60 pedicles in total. To define trajectories for a given patient, sparse deformation fields from the atlas surfaces to the input (CT or MR image) are applied on the annotated trajectories. Mean value coordinates are used to interpolate dense deformation fields. The pose of a straight trajectory is optimized by image-based registration to an accumulated volume of the deformed annotations. For evaluation, input deformation fields were created using coherent point drift (CPD) to perform a leave-one-out analysis over the atlas surfaces. CPD registration demonstrated surface error of 0.89 ± 0.10 mm (median ± interquartile range) for T7/T8 and 1.29 ± 0.15 mm for L3. At the pedicle center, registered trajectories deviated from the expert reference by 0.56 ± 0.63 mm (T7/T8) and 1.12 ± 0.67 mm (L3). The predicted maximum screw diameter differed by 0.45 ± 0.62 mm (T7/T8), and 1.26 ± 1.19 mm (L3). The automated planning method avoided screw collisions in all cases and demonstrated close agreement overall with expert reference plans, offering a potentially valuable tool in support of surgical guidance and QA.

OBJECTIVEMyelopathy selectively involving the lower extremities can occur secondary to spondylotic changes, tumor, vascular malformations, or thoracolumbar cord ischemia. Vascular causes of myelopathy are rarely described. An uncommon etiology within this category is diaphragmatic crus syndrome, in which compression of an intersegmental artery supplying the cord leads to myelopathy. The authors present the operative technique for treating this syndrome, describing their experience with 3 patients treated for acute-onset lower-extremity myelopathy secondary to hypoperfusion of the anterior spinal artery.METHODSAll patients had compression of a lumbar intersegmental artery supplying the cord; the compression was caused by the diaphragmatic crus. Compression of the intersegmental artery was probably producing the patients’ symptoms by decreasing blood flow through the artery of Adamkiewicz, causing lumbosacral ischemia.RESULTSAll patients underwent surgery to transect the offending diaphragmatic crus. Each patient experienced substantial symptom improvement, and 2 patients made a full neurological recovery before discharge.CONCLUSIONSDiaphragmatic crus syndrome is a rare or under-recognized cause of ischemic myelopathy. Patients present with episodic acute-on-chronic lower-extremity paraparesis, gait instability, and numbness. Angiography confirms compression of an intersegmental artery that gives rise to a dominant radiculomedullary artery. Transecting the offending diaphragmatic crus can produce complete resolution of neurological symptoms.

Accurate intraoperative localization of target anatomy and adjacent nervous and vascular tissue is essential to safe, effective surgery, and multimodality deformable registration can be used to identify such anatomy by fusing preoperative CT or MR images with intraoperative images. A deformable image registration method has been developed to estimate viscoelastic diffeomorphisms between preoperative MR and intraoperative CT using modality-independent neighborhood descriptors (MIND) and a Huber metric for robust registration. The method, called MIND Demons, optimizes a constrained symmetric energy functional incorporating priors on smoothness, geodesics, and invertibility by alternating between Gauss-Newton optimization and Tikhonov regularization in a multiresolution scheme. Registration performance was evaluated for the MIND Demons method with a symmetric energy formulation in comparison to an asymmetric form, and sensitivity to anisotropic MR voxel-size was analyzed in phantom experiments emulating image-guided spine-surgery in comparison to a free-form deformation (FFD) method using local mutual information (LMI). Performance was validated in a clinical study involving 15 patients undergoing intervention of the cervical, thoracic, and lumbar spine. The target registration error (TRE) for the symmetric MIND Demons formulation (1.3 ± 0.8 mm (median ± interquartile)) outperformed the asymmetric form (3.6 ± 4.4 mm). The method demonstrated fairly minor sensitivity to anisotropic MR voxel size, with median TRE ranging 1.3-2.9 mm for MR slice thickness ranging 0.9-9.9 mm, compared to TRE = 3.2-4.1 mm for LMI FFD over the same range. Evaluation in clinical data demonstrated sub-voxel TRE (

Background Even though virtually all patients with Ewing sarcoma achieve a radiographic complete response, up to 30% of patients who present with localized disease and up to 90% of those who present with metastases experience a metastatic disease recurrence, highlighting the inability to identify patients with residual disease at the end of therapy. Up to 95% of Ewing sarcomas carry a driving EWS-ETS translocation that has an intronic breakpoint that is specific to each tumor, and the authors developed a system to quantitatively detect the specific breakpoint DNA fragment in patient plasma. Methods The authors used a long-range multiplex polymerase chain reaction (PCR) technique to identify tumor-specific EWS-ETS breakpoints in Ewing sarcoma cell lines, patient-derived xenografts, and patient tumors, and this sequence was used to design tumor-specific primer sets to detect plasma tumor DNA (ptDNA) by droplet digital PCR in xenograft-bearing mice and patients. Results Tumor-specific breakpoint DNA fragments were detected in the plasma of xenograft-bearing mice, and the signal correlated with tumor burden during primary tumor growth, after surgical resection, and at the time of metastatic disease recurrence. Furthermore, the authors were able to detect the specific breakpoint in plasma DNA obtained from 3 patients with Ewing sarcoma and in 2 patients the authors were able to detect ptDNA when there was radiographically undetectable disease present. Conclusions The use of droplet digital PCR to detect tumor-specific EWS-ETS fusion gene breakpoint ptDNA fragments can be developed into a highly personalized biomarker of disease recurrence that can be optimized in animal studies for ultimate use in patients. Cancer 2016;122:3015-3023. © 2016 American Cancer Society.

In image-guided spine surgery, robust three-dimensional to two-dimensional (3D-2D) registration of preoperative computed tomography (CT) and intraoperative radiographs can be challenged by the image content mismatch associated with the presence of surgical instrumentation and implants as well as soft-tissue resection or deformation. This work investigates image similarity metrics in 3D-2D registration offering improved robustness against mismatch, thereby improving performance and reducing or eliminating the need for manual masking. The performance of four gradient-based image similarity metrics (gradient information (GI), gradient correlation (GC), gradient information with linear scaling (GS), and gradient orientation (GO)) with a multi-start optimization strategy was evaluated in an institutional review board-approved retrospective clinical study using 51 preoperative CT images and 115 intraoperative mobile radiographs. Registrations were tested with and without polygonal masks as a function of the number of multistarts employed during optimization. Registration accuracy was evaluated in terms of the projection distance error (PDE) and assessment of failure modes (PDE 30 mm) that could impede reliable vertebral level localization. With manual polygonal masking and 200 multistarts, the GC and GO metrics exhibited robust performance with 0% gross failures and median PDE6.4 mm (±4.4 mm interquartile range (IQR)) and a median runtime of 84 s (plus upwards of 1-2 min for manual masking). Excluding manual polygonal masks and decreasing the number of multistarts to 50 caused the GC-based registration to fail at a rate of14%; however, GO maintained robustness with a 0% gross failure rate. Overall, the GI, GC, and GS metrics were susceptible to registration errors associated with content mismatch, but GO provided robust registration (median PDE = 5.5 mm, 2.6 mm IQR) without manual masking and with an improved runtime (29.3 s). The GO metric improved the registration accuracy and robustness in the presence of strong image content mismatch. This capability could offer valuable assistance and decision support in spine level localization in a manner consistent with clinical workflow.

Recent work has yielded a method for automatic labeling of vertebrae in intraoperative radiographs as an assistant to manual level counting. The method, called LevelCheck, previously demonstrated promise in phantom studies and retrospective studies. This study aims to: (#1) Analyze the effect of LevelCheck on accuracy and confidence of localization in two modes: (a) Independent Check (labels displayed after the surgeon’s decision) and (b) Active Assistant (labels presented before the surgeon’s decision). (#2) Assess the feasibility and utility of LevelCheck in the operating room. Two studies were conducted: a laboratory study investigating these two workflow implementations in a simulated operating environment with 5 surgeons, reviewing 62 cases selected from a dataset of radiographs exhibiting a challenge to vertebral localization; and a clinical study involving 20 patients undergoing spine surgery. In Study #1, the median localization error without assistance was 30.4% (IQR = 5.2%) due to the challenging nature of the cases. LevelCheck reduced the median error to 2.4% for both the Independent Check and Active Assistant modes (p

OBJECT Spinal metastases from gynecological cancers are rare, with few cases reported in the literature. In this study, the authors examine a series of patients with spinal metastases from gynecological cancer and review the literature. METHODS The cases of 6 consecutive patients who underwent spine surgery for metastatic gynecological cancer between 2007 and 2012 at a single institution were retrospectively reviewed. The recorded demographic, operative, and postoperative factors were reviewed, and the functional outcomes were determined by change in Karnofsky Performance Scale and the American Spine Injury Association (ASIA) score during follow-up. A systematic review of the literature was also performed to evaluate outcomes for patients with similar gynecological metastases to the spine. RESULTS In this series, details regarding metastatic gynecological cancers to the spine are as follows: 2 patients with cervical cancer (both presented at age 46 years, mean postoperative survival of 32 months), 2 patients with endometrial cancer (mean age of 40 years, mean postoperative survival of 26 months), and 2 patients with leiomyosarcoma (mean age of 44 years, mean postoperative survival of 20 months). All patients presented with pain, and no complications were noted following surgery. All patients with known follow-up had stable or improved neurological outcomes, performance status, and improved pain, without local recurrence of tumor. Overall median survival after diagnosis of metastatic spine lesions for all cases in the literature as well as those treated by the authors was 15 months. When categorized by type, median survival of patients with cervical cancer (n = 2), endometrial cancer (n = 26), and leiomyosarcoma (n = 16) was 32, 10, and 22.5 months, respectively. CONCLUSIONS Gynecological cancers metastasizing to the spine are rare. In this series, overall survival following diagnosis of spinal metastasis and surgery was 27 months, with cervical cancer, endometrial cancer, and leiomyosarcoma survival being 32, 26, and 20 months, respectively. Combined with literature cases, survival differs depending on primary histology, with decreasing survival from cervical cancer (32 months) to leiomyosarcoma (22.5 months) to endometrial cancer (10 months). Integrating such information with other patient factors may more accurately guide decision making regarding management of such spinal lesions.

Giant cell tumors (GCTs) are rare primary bone neoplasms. The best long-term prognosis is achieved via complete tumor excision, but this feat is challenging in the spine due to proximity of blood vessels and nervous tissue. When occurring in the sacrum, GCTs have been removed in an en bloc fashion via combined anterior/posterior approaches, oftentimes with nerve root sacrifice. The purpose of this article is to present a case of a single-staged, posterior-only approach for en bloc resection of a sacral GCT without nerve root sacrifice.A 45-year-old female presented with intractable lower back and leg pain, saddle anesthesia, and lower extremity weakness. She underwent imaging studies, which revealed a lesion involving the S1 and S2 vertebral bodies. Computed tomography guided biopsy revealed the lesion to be a GCT. The patient underwent a posterior-only approach without nerve root sacrifice to achieve an en bloc resection, followed by lumbopelvic reconstruction.Sacrectomy via a single-staged posterior approach with nerve root preservation is a challenging yet feasible procedure for the treatment of giant cell tumors in carefully selected patients.

Cell-free DNA shed by cancer cells has been shown to be a rich source of putative tumor-specific biomarkers. Because cell-free DNA from brain and spinal cord tumors cannot usually be detected in the blood, we studied whether the cerebrospinal fluid (CSF) that bathes the CNS is enriched for tumor DNA, here termed CSF-tDNA. We analyzed 35 primary CNS malignancies and found at least one mutation in each tumor using targeted or genome-wide sequencing. Using these patient-specific mutations as biomarkers, we identified detectable levels of CSF-tDNA in 74% [95% confidence interval (95% CI) = 57-88%] of cases. All medulloblastomas, ependymomas, and high-grade gliomas that abutted a CSF space were detectable (100% of 21 cases; 95% CI = 88-100%), whereas no CSF-tDNA was detected in patients whose tumors were not directly adjacent to a CSF reservoir (P0.0001, Fisher's exact test). These results suggest that CSF-tDNA could be useful for the management of patients with primary tumors of the brain or spinal cord.

OBJECT Clinical outcomes in patients with primary spinal osteochondromas are limited to small series and sporadic case reports. The authors present data on the first long-term investigation of spinal osteochondroma cases. METHODS An international, multicenter ambispective study on primary spinal osteochondroma was performed. Patients were included if they were diagnosed with an osteochondroma of the spine and received surgical treatment between October 1996 and June 2012 with at least 1 follow-up. Perioperative prognostic variables, including patient age, tumor size, spinal level, and resection, were analyzed in reference to long-term local recurrence and survival. Tumor resections were compared using Enneking appropriate (EA) or Enneking inappropriate surgical margins. RESULTS Osteochondromas were diagnosed in 27 patients at an average age of 37 years. Twenty-two lesions were found in the mobile spine (cervical, thoracic, or lumbar) and 5 in the fixed spine (sacrum). Twenty-three cases (88%) were benign tumors (Enneking tumor Stages 1–3), whereas 3 (12%) exhibited malignant changes (Enneking tumor Stages IA–IIB). Sixteen patients (62%) underwent en bloc treatment—that is, wide or marginal resection—and 10 (38%) underwent intralesional resection. Twenty-four operations (92%) followed EA margins. No one received adjuvant therapy. Two patients (8%) experienced recurrences: one in the fixed spine and one in the mobile spine. Both recurrences occurred in latent Stage 1 tumors following en bloc resection. No osteochondroma-related deaths were observed. CONCLUSIONS In the present study, most patients underwent en bloc resection and were treated as EA cases. Both recurrences occurred in the Stage 1 tumor cohort. Therefore, although benign in character, osteochondromas still require careful management and thorough follow-up.

Study Design Retrospective study. Objective Our objective was to identify preoperative prognostic factors associated with survival in patients with spinal metastasis from lung carcinoma. Methods A retrospective analysis of 26 patients diagnosed with lung carcinoma metastatic to the spinal column was performed to determine factors associated with survival. We used 3 months survival as the clinical cutoff for whether surgical intervention should be performed. We analyzed patients who survived less than 3 months compared with those who survived more than 3 months. Demographic, preoperative, operative, and postoperative factors including functional scores were collected for analysis. Results The median survival for all patients in our study was 3.5 months. We found a statistically significant difference between the group that survived less than 3 months and the group that survived greater than 3 months in terms of extrathoracic metastasis, visceral metastasis, and average postoperative modified Rankin score. Conclusion Determining which patients with lung cancer spinal metastases will benefit from surgical intervention is often dictated by the patient's predicted life expectancy. Factors associated with poorer prognosis include age, functional status, visceral metastases, and extrathoracic metastases. Although the prognosis for patients with lung cancer spinal metastases is poor, some patients may experience long-term benefit from surgical intervention.

A 3-dimensional-2-dimensional (3D-2D) image registration algorithm, "LevelCheck," was used to automatically label vertebrae in intraoperative mobile radiographs obtained during spine surgery. Accuracy, computation time, and potential failure modes were evaluated in a retrospective study of 20 patients.To measure the performance of the LevelCheck algorithm using clinical images acquired during spine surgery.In spine surgery, the potential for wrong level surgery is significant due to the difficulty of localizing target vertebrae based solely on visual impression, palpation, and fluoroscopy. To remedy this difficulty and reduce the risk of wrong-level surgery, our team introduced a program (dubbed LevelCheck) to automatically localize target vertebrae in mobile radiographs using robust 3D-2D image registration to preoperative computed tomographic (CT) scan.Twenty consecutive patients undergoing thoracolumbar spine surgery, for whom both a preoperative CT scan and an intraoperative mobile radiograph were available, were retrospectively analyzed. A board-certified neuroradiologist determined the "true" vertebra levels in each radiograph. Registration of the preoperative CT scan to the intraoperative radiograph was calculated via LevelCheck, and projection distance errors were analyzed. Five hundred random initializations were performed for each patient, and algorithm settings (viz, the number of robust multistarts, ranging 50-200) were varied to evaluate the trade-off between registration error and computation time. Failure mode analysis was performed by individually analyzing unsuccessful registrations (5 mm distance error) observed with 50 multistarts.At 200 robust multistarts (computation time of ∼26 s), the registration accuracy was 100% across all 10,000 trials. As the number of multistarts (and computation time) decreased, the registration remained fairly robust, down to 99.3% registration accuracy at 50 multistarts (computation time ∼7 s).The LevelCheck algorithm correctly identified target vertebrae in intraoperative mobile radiographs of the thoracolumbar spine, demonstrating acceptable computation time, compatibility with routinely obtained preoperative CT scans, and warranting investigation in prospective studies.N/A.

Percutaneous pelvic screw placement is challenging due to narrow bone corridors surrounded by vulnerable structures and difficult visual interpretation of complex anatomical shapes in 2D x-ray projection images. To address these challenges, a system for planning, guidance, and quality assurance (QA) is presented, providing functionality analogous to surgical navigation, but based on robust 3D-2D image registration techniques using fluoroscopy images already acquired in routine workflow. Two novel aspects of the system are investigated: automatic planning of pelvic screw trajectories and the ability to account for deformation of surgical devices (K-wire deflection). Atlas-based registration is used to calculate a patient-specific plan of screw trajectories in preoperative CT. 3D-2D registration aligns the patient to CT within the projective geometry of intraoperative fluoroscopy. Deformable known-component registration (dKC-Reg) localizes the surgical device, and the combination of plan and device location is used to provide guidance and QA. A leave-one-out analysis evaluated the accuracy of automatic planning, and a cadaver experiment compared the accuracy of dKC-Reg to rigid approaches (e.g., optical tracking). Surgical plans conformed within the bone cortex by 3–4 mm for the narrowest corridor (superior pubic ramus) and >5 mm for the widest corridor (tear drop). The dKC-Reg algorithm localized the K-wire tip within 1.1 mm and 1.4° and was consistently more accurate than rigid-body tracking (errors up to 9 mm). The system was shown to automatically compute reliable screw trajectories and accurately localize deformed surgical devices (K-wires). Such capability could improve guidance and QA in orthopaedic surgery, where workflow is impeded by manual planning, conventional tool trackers add complexity and cost, rigid tool assumptions are often inaccurate, and qualitative interpretation of complex anatomy from 2D projections is prone to trial-and-error with extended fluoroscopy time.

Study Design: Retrospective cohort study. Objective: The S2-alar-iliac (S2AI) technique has been described as an alternative method for pelvic fixation in place of iliac screws (ISs) in spinal deformity surgery. The objective of this study was to analyze the impact of S2AI screws on radiographical outcomes, including spinopelvic parameters. Methods: A retrospective review of 17 patients receiving ISs and 46 patients receiving S2AI screws for correction of adult spinal deformity between 2010 and 2015 with minimum 1-year follow-up was conducted. Patient data on postoperative complications, including reoperation rates and proximal junctional kyphosis (PJK), and radiographical parameters was collected and statistically analyzed. Results: With mean follow-up of 21.1 months, the overall reoperation rate was significantly lower in the S2AI group than in the IS group (21.7% vs 58.8%, P = .01), but the incidence of PJK was similar (32.6% vs 35.3%, P > .99). Moreover, the time to reoperation in the IS group was significantly shorter than in the S2AI group (P = .001), and the S2AI group trended toward a longer time to reoperation due to PJK (P = .08). There was a significantly higher change in pelvic incidence (PI) in the S2AI group (−6.0°) compared with the IS group (P = .001). Conclusions: Compared with the IS technique, the S2AI technique demonstrated a lower rate of overall reoperation, a similar rate of PJK, longer time to reoperation, and possible reduction in PI. Future studies may be warranted to clarify the mechanism of these results and how they can be translated into improved patient care.

A multi-stage image-based 3D-2D registration method is presented that maps annotations in a 3D image (e.g. point labels annotating individual vertebrae in preoperative CT) to an intraoperative radiograph in which the patient has undergone non-rigid anatomical deformation due to changes in patient positioning or due to the intervention itself. The proposed method (termed msLevelCheck) extends a previous rigid registration solution (LevelCheck) to provide an accurate mapping of vertebral labels in the presence of spinal deformation. The method employs a multi-stage series of rigid 3D-2D registrations performed on sets of automatically determined and increasingly localized sub-images, with the final stage achieving a rigid mapping for each label to yield a locally rigid yet globally deformable solution. The method was evaluated first in a phantom study in which a CT image of the spine was acquired followed by a series of 7 mobile radiographs with increasing degree of deformation applied. Second, the method was validated using a clinical data set of patients exhibiting strong spinal deformation during thoracolumbar spine surgery. Registration accuracy was assessed using projection distance error (PDE) and failure rate (PDE 20 mm-i.e. label registered outside vertebra). The msLevelCheck method was able to register all vertebrae accurately for all cases of deformation in the phantom study, improving the maximum PDE of the rigid method from 22.4 mm to 3.9 mm. The clinical study demonstrated the feasibility of the approach in real patient data by accurately registering all vertebral labels in each case, eliminating all instances of failure encountered in the conventional rigid method. The multi-stage approach demonstrated accurate mapping of vertebral labels in the presence of strong spinal deformation. The msLevelCheck method maintains other advantageous aspects of the original LevelCheck method (e.g. compatibility with standard clinical workflow, large capture range, and robustness against mismatch in image content) and extends capability to cases exhibiting strong changes in spinal curvature.

Pelvic Kirschner wire (K-wire) insertion is a challenging surgical task requiring interpretation of complex 3D anatomical shape from 2D projections (fluoroscopy) and delivery of device trajectories within fairly narrow bone corridors in proximity to adjacent nerves and vessels. Over long trajectories (~10-25 cm), K-wires tend to curve (deform), making conventional rigid navigation inaccurate at the tip location. A system is presented that provides accurate 3D localization and guidance of rigid or deformable surgical devices (“components” – e.g., K-wires) based on 3D-2D registration. The patient is registered to a preoperative CT image by virtually projecting digitally reconstructed radiographs (DRRs) and matching to two or more intraoperative x-ray projections. The K-wire is localized using an analogous procedure matching DRRs of a deformably parametrized model for the device component (deformable known-component registration, or dKC-Reg). A cadaver study was performed in which a K-wire trajectory was delivered in the pelvis. The system demonstrated target registration error (TRE) of 2.1 ± 0.3 mm in location of the K-wire tip (median ± interquartile range, IQR) and 0.8 ± 1.4o in orientation at the tip (median ± IQR), providing functionality analogous to surgical tracking / navigation using imaging systems already in the surgical arsenal without reliance on a surgical tracker. The method offers quantitative 3D guidance using images (e.g., inlet / outlet views) already acquired in the standard of care, potentially extending the advantages of navigation to broader utilization in trauma surgery to improve surgical precision and safety.

Introduction: Fluoroscopically guided procedures often involve repeated acquisitions for C-arm positioning at the cost of radiation exposure and time in the operating room. A virtual fluoroscopy system is reported with the potential of reducing dose and time spent in C-arm positioning, utilizing three key advances: robust 3D-2D registration to a preoperative CT; real-time forward projection on GPU; and a motorized mobile C-arm with encoder feedback on C-arm orientation. Method: Geometric calibration of the C-arm was performed offline in two rotational directions (orbit α, orbit β). Patient registration was performed using image-based 3D-2D registration with an initially acquired radiograph of the patient. This approach for patient registration eliminated the requirement for external tracking devices inside the operating room, allowing virtual fluoroscopy using commonly available systems in fluoroscopically guided procedures within standard surgical workflow. Geometric accuracy was evaluated in terms of projection distance error (PDE) in anatomical fiducials. A pilot study was conducted to evaluate the utility of virtual fluoroscopy to aid C-arm positioning in image guided surgery, assessing potential improvements in time, dose, and agreement between the virtual and desired view. Results: The overall geometric accuracy of DRRs in comparison to the actual radiographs at various C-arm positions was PDE (mean ± std) = 1.6 ± 1.1 mm. The conventional approach required on average 8.0 ± 4.5 radiographs spent “fluoro hunting” to obtain the desired view. Positioning accuracy improved from 2.6o ± 2.3o (in α) and 4.1o ± 5.1o (in β) in the conventional approach to 1.5o ± 1.3o and 1.8o ± 1.7o, respectively, with the virtual fluoroscopy approach. Conclusion: Virtual fluoroscopy could improve accuracy of C-arm positioning and save time and radiation dose in the operating room. Such a system could be valuable to training of fluoroscopy technicians as well as intraoperative use in fluoroscopically guided procedures.

OBJECTIVE With the advent of new adjunctive therapy, the overall survival of patients harboring spinal column tumors has improved. However, there is limited knowledge regarding the optimal bone graft options following resection of spinal column tumors, due to their relative rarity and because fusion outcomes in this cohort are affected by various factors, such as radiation therapy (RT) and chemotherapy. Furthermore, bone graft options are often limited following tumor resection because the use of local bone grafts and bone morphogenetic proteins (BMPs) are usually avoided in light of microscopic infiltration of tumors into local bone and potential carcinogenicity of BMP. The objective of this study was to review and meta-analyze the relevant clinical literature to provide further clinical insight regarding bone graft options. METHODS A web-based MEDLINE search was conducted in accordance with preferred reporting items for systematic review and meta-analysis (PRISMA) guidelines, which yielded 27 articles with 383 patients. Information on baseline characteristics, tumor histology, adjunctive treatments, reconstruction methods, bone graft options, fusion rates, and time to fusion were collected. Pooled fusion rates (PFRs) and I2 values were calculated in meta-analysis. Meta-regression analyses were also performed if each variable appeared to affect fusion outcomes. Furthermore, data on 272 individual patients were available, which were additionally reviewed and statistically analyzed. RESULTS Overall, fusion rates varied widely from 36.0% to 100.0% due to both inter- and intrastudy heterogeneity, with a PFR of 85.7% (I2 = 36.4). The studies in which cages were filled with morselized iliac crest autogenic bone graft (ICABG) and/or other bone graft options were used for anterior fusion showed a significantly higher PFR of 92.8, compared with the other studies (83.3%, p = 0.04). In per-patient analysis, anterior plus posterior fusion resulted in a higher fusion rate than anterior fusion only (98.8% vs 86.4%, p < 0.001). Although unmodifiable, RT (90.3% vs 98.6%, p = 0.03) and lumbosacral tumors (74.6% vs 97.9%, p < 0.001) were associated with lower fusion rates in univariate analysis. The mean time to fusion was 5.4 ± 1.4 months (range 3–9 months), whereas 16 of 272 patients died before the confirmation of solid fusion with a mean survival of 3.1 ± 2.1 months (range 0.5–6 months). The average time to fusion of patients who received RT and chemotherapy were significantly longer than those who did not receive these adjunctive treatments (RT: 6.1 months vs 4.3 months, p < 0.001; chemotherapy: 6.0 months vs 4.3 months, p = 0.02). CONCLUSIONS Due to inter- and intrastudy heterogeneity in patient, disease, fusion criteria, and treatment characteristics, the optimal surgical techniques and factors predictive of fusion remain unclear. Clearly, future prospective, randomized studies will be necessary to better understand the issues surrounding bone graft selection following resection of spinal column tumors.

STUDY DESIGN An automatic radiographic labeling algorithm called "LevelCheck" was analyzed as a means of decision support for target localization in spine surgery. The potential clinical utility and scenarios in which LevelCheck is likely to be the most beneficial were assessed in a retrospective clinical data set (398 cases) in terms of expert consensus from a multi-reader study (three spine surgeons). OBJECTIVE The aim of this study was to evaluate the potential utility of the LevelCheck algorithm for vertebrae localization. SUMMARY OF BACKGROUND DATA Three hundred ninety-eight intraoperative radiographs and 178 preoperative computed tomographic (CT) images for patients undergoing spine surgery in cervical, thoracic, lumbar regions. METHODS Vertebral labels annotated in preoperative CT image were overlaid on intraoperative radiographs via 3D-2D registration. Three spine surgeons assessed the radiographs and LevelCheck labeling according to a questionnaire evaluating performance, utility, and suitability to surgical workflow. Geometric accuracy and registration run time were measured for each case. RESULTS LevelCheck was judged to be helpful in 42.2% of the cases (168/398), to improve confidence in 30.6% of the cases (122/398), and in no case diminished performance (0/398), supporting its potential as an independent check and assistant to decision support in spine surgery. The clinical contexts for which the method was judged most likely to be beneficial included the following scenarios: images with a lack of conspicuous anatomical landmarks; level counting across long spine segments; vertebrae obscured by other anatomy (e.g., shoulders); poor radiographic image quality; and anatomical variations/abnormalities. The method demonstrated 100% geometric accuracy (i.e., overlaid labels within the correct vertebral level in all cases) and did not introduce ambiguity in image interpretation. CONCLUSION LevelCheck is a potentially useful means of decision support in vertebral level localization in spine surgery. LEVEL OF EVIDENCE N/A.

Purpose/objectives The complex planning and quality assurance required for spine SBRT are a barrier to implementation in time-sensitive or limited resource clinical situations. We developed and validated an automated inverse planning algorithm designed to streamline planning and allow rapid delivery of conformal single fraction spine SBRT using widely available technology. Materials/methods The Rapid Spine (RaSp) automated script successfully generated single fraction SBRT plans for fourteen complex spinal lesions previously treated at a single high-volume institution. Automated RaSp plans were limited to 5 beams with a total of 15 segments (allowing calculation-based verification) and optimized based on RTOG 0631 objectives. Standard single fraction (16 Gy) stereotactic IMRT plans were generated for the same set of complex spinal lesions and used for comparison. A conservative 2 mm posterior isocenter shift was used to simulate minor set-up error. Results Automated plans were generated in under 5 min from target definition and had a mean dose to the PTV of 1663 cGy (SD 131.5), a dose to 90 % of PTV (D90) of 1358 cGy (SD 111.0), and a maximum point dose (Dmax) to the PTV of 2055 cGy (SD 195.2) on average. IMRT plans took longer to generate but yielded more favorable dose escalation with a mean dose to the PTV of 1891 cGy (SD 117.6), D90 of 1731 cGy (SD 126.5), and Dmax of 2218 cGy (SD 195.7). A 2 mm posterior shift resulted in a 20 % (SD 10.5 %) increase in cord dose for IMRT plans and a 10 % (SD 5.3 %) increase for RaSp plans. The 2 mm perturbation caused 3 cord dose violations for the IMRT plans and 1 violation for corresponding RaSp plans. Conclusion The Rapid Spine plan method yields timely and dosimetrically reasonable SBRT plans which meet RTOG 0631 objectives and are suitable for rapid yet robust pretreatment quality assurance followed by expedited treatment delivery. RaSp plans reduce the tradeoff between rapid treatment and optimal dosimetry in urgent cases and limited resource situations.

While several approaches have been suggested for performing a transthoracic corpectomy of the thoracolumbar spine, the steep learning curve and high risk of operative morbidity often dissuades its use clinically. As a result, posterior approaches have been more frequently used, though transthoracic approaches often allow for improved access for more complete decompression of the spinal cord. Additionally, the transthoracic approach allows for more complete removal of vertebral body lesions along with better access for reconstruction of the anterior column. Here we describe a distinct nine-step thoracolumbar corpectomy technique via a transthoracic approach. We include a description of one patient with one-year follow-up to further illustrate the surgical approach and relevant surgical anatomy. We have used this technique for maximal bi-pedicular decompression afforded by the lateral approach. We discuss key anatomical considerations, perioperative techniques and potential complications of the operation. The presented nine-step transthoracic corpectomy technique is a safe method for providing adequate neurological decompression and vertebral body tumor removal.

Intraoperative localization of target anatomy and critical structures defined in preoperative MR/CT images can be achieved through the use of multimodality deformable registration. We propose a symmetric diffeomorphic deformable registration algorithm incorporating a modality-independent neighborhood descriptor (MIND) and a robust Huber metric for MR-to-CT registration. The method, called MIND Demons, finds a deformation field between two images by optimizing an energy functional that incorporates both the forward and inverse deformations, smoothness on the integrated velocity fields, a modality-insensitive similarity function suitable to multimodality images, and smoothness on the diffeomorphisms themselves. Direct optimization without relying on the exponential map and stationary velocity field approximation used in conventional diffeomorphic Demons is carried out using a Gauss-Newton method for fast convergence. Registration performance and sensitivity to registration parameters were analyzed in simulation, phantom experiments, and clinical studies emulating application in image-guided spine surgery, and results were compared to mutual information (MI) free-form deformation (FFD), local MI (LMI) FFD, normalized MI (NMI) Demons, and MIND with a diffusion-based registration method (MIND-elastic). The method yielded sub-voxel invertibility (0.008 mm) and nonzero-positive Jacobian determinants. It also showed improved registration accuracy in comparison to the reference methods, with mean target registration error (TRE) of 1.7 mm compared to 11.3, 3.1, 5.6, and 2.4 mm for MI FFD, LMI FFD, NMI Demons, and MIND-elastic methods, respectively. Validation in clinical studies demonstrated realistic deformations with sub-voxel TRE in cases of cervical, thoracic, and lumbar spine.

During spinal neurosurgery, patient-specific information, planning, and annotation such as vertebral labels can be mapped from preoperative 3D CT to intraoperative 2D radiographs via image-based 3D-2D registration. Such registration has been shown to provide a potentially valuable means of decision support in target localization as well as quality assurance of the surgical product. However, robust registration can be challenged by mismatch in image content between the preoperative CT and intraoperative radiographs, arising, for example, from anatomical deformation or the presence of surgical tools within the radiograph. In this work, we develop and evaluate methods for automatically mitigating the effect of content mismatch by leveraging the surgical planning data to assign greater weight to anatomical regions known to be reliable for registration and vital to the surgical task while removing problematic regions that are highly deformable or often occluded by surgical tools. We investigated two approaches to assigning variable weight (i.e., "masking") to image content and/or the similarity metric: (1) masking the preoperative 3D CT ("volumetric masking"); and (2) masking within the 2D similarity metric calculation ("projection masking"). The accuracy of registration was evaluated in terms of projection distance error (PDE) in 61 cases selected from an IRB-approved clinical study. The best performing of the masking techniques was found to reduce the rate of gross failure (PDE > 20 mm) from 11.48% to 5.57% in this challenging retrospective data set. These approaches provided robustness to content mismatch and eliminated distinct failure modes of registration. Such improvement was gained without additional workflow and has motivated incorporation of the masking methods within a system under development for prospective clinical studies.

Purpose: Localization of target anatomy and critical structures defined in preoperative MR images can be achieved by means of multi-modality deformable registration to intraoperative CT. We propose a symmetric diffeomorphic deformable registration algorithm incorporating a modality independent neighborhood descriptor (MIND) and a robust Huber metric for MR-to-CT registration. Method: The method, called MIND Demons, solves for the deformation field between two images by optimizing an energy functional that incorporates both the forward and inverse deformations, smoothness on the velocity fields and the diffeomorphisms, a modality-insensitive similarity function suitable to multi-modality images, and constraints on geodesics in Lagrangian coordinates. Direct optimization (without relying on an exponential map of stationary velocity fields used in conventional diffeomorphic Demons) is carried out using a Gauss-Newton method for fast convergence. Registration performance and sensitivity to registration parameters were analyzed in simulation, in phantom experiments, and clinical studies emulating application in image-guided spine surgery, and results were compared to conventional mutual information (MI) free-form deformation (FFD), local MI (LMI) FFD, and normalized MI (NMI) Demons. Result: The method yielded sub-voxel invertibility (0.006 mm) and nonsingular spatial Jacobians with capability to preserve local orientation and topology. It demonstrated improved registration accuracy in comparison to the reference methods, with mean target registration error (TRE) of 1.5 mm compared to 10.9, 2.3, and 4.6 mm for MI FFD, LMI FFD, and NMI Demons methods, respectively. Validation in clinical studies demonstrated realistic deformation with sub-voxel TRE in cases of cervical, thoracic, and lumbar spine. Conclusions: A modality-independent deformable registration method has been developed to estimate a viscoelastic diffeomorphic map between preoperative MR and intraoperative CT. The method yields registration accuracy suitable to application in image-guided spine surgery across a broad range of anatomical sites and modes of deformation.

OBJECTIVE The purpose of this study was to report the long-term clinical outcomes following 3- and 4-level anterior cervical discectomy and fusion (ACDF). METHODS A retrospective review of all adult neurosurgical patients undergoing elective ACDF for degenerative disease at a single institution between 1996 and 2013 was performed. Patients who underwent first-time 3- or 4-level ACDF were included; patients with previous cervical spine surgery, those undergoing anterior/posterior approaches, and those with corpectomy were excluded. Outcome measures included perioperative complication rates, fusion rates, need for revision surgery, Nurick Scores, Odom's criteria, symptom resolution, neck visual analog scale (VAS) pain score, and persistent narcotics usage. RESULTS Seventy-one patients who underwent 3-level ACDF and 26 patients who underwent 4-level ACDF were identified and followed for an average of 7.6 ± 4.2 years. There was 1 case (3.9%) of deep wound infection in the 4-level group and 1 case in the 3-level group (1.4%; p = 0.454). Postoperatively, 31% of patients in the 4-level group complained of dysphagia, compared with 12.7% in the 3-level group (p = 0.038). The fusion rate was 84.6% after 4-level ACDF and 94.4% after 3-level ACDF (p = 0.122). At last follow-up, a significantly higher proportion of patients in the 4-level group continued to have axial neck pain (53.8%) than in the 3-level group (31%; p = 0.039); the daily oral morphine equivalent dose was significantly higher in the 4-level group (143 ± 97 mg/day) than in the 3-level group (25 ± 10 mg/day; p = 0.030). Outcomes based on Odom's criteria were also different between cohorts (p = 0.044), with a significantly lower proportion of patients in the 4-level ACDF group experiencing an excellent/good outcome. CONCLUSIONS In this study, patients who underwent 4-level ACDF had significantly higher rates of dysphagia, postoperative neck pain, and postoperative narcotic usage when compared with patients who underwent 3-level ACDF. Pseudarthrosis and deep wound infection rates were also higher in the 4-level group, although this did not reach statistical significance. Additionally, a smaller proportion of patients achieved a good/excellent outcome in the 4-level group than in the 3-level group. These findings suggest a significant increase of perioperative morbidity and worsened outcomes for patients who undergo 4- versus 3-level ACDF.

ObjectAdvocates of minimally invasive discectomy (MID) have promoted this operation as an alternative to open discectomy (OD), arguing that there may be less injury to the paraspinal muscles, decreased postoperative pain, and a faster recovery time. However, a recently published large randomized controlled trial (RCT) comparing these approaches reported inferior relief of leg pain in patients undergoing MID. The authors conducted a meta-analysis to evaluate complications and improvement in leg pain in patients with radiculopathy enrolled in RCTs comparing OD to MID.MethodsThe authors performed a literature search using Medline and EMBASE of studies indexed between January 1990 and January 2011. Predetermined RCT eligibility included the usage of tubular retractors during MID, a minimum follow-up duration of 1 year, and quantification of pain with the visual analog scale (VAS). Trials that only evaluated patients with recurrent disc herniation were excluded. Data on operative parameters, complications, and VAS scores of leg pain were extracted by 2 investigators. A meta-analysis was performed assuming random effects to determine the difference in mean change for continuous outcomes and the risk ratio for binary outcomes.ResultsSix trials comprising 837 patients (of whom 388 were randomized to MID and 449 were randomized to OD) were included. The mean operative time was 49 minutes during MID and 44 minutes during OD; this difference was not statistically significant. Incidental durotomies occurred significantly more frequently during MID (5.67% compared with 2.90% for OD; RR 2.05, 95% CI 1.05–3.98). Intraoperative complications (incidental durotomies and nerve root injuries) were also significantly more common in patients undergoing MID (RR 2.01, 95% CI 1.07–3.77). The mean preoperative VAS score for leg pain was 6.9 in patients randomized to MID and 7.2 in those randomized to OD. With long-term follow-up (1–2 years postoperatively), the mean VAS score improved to 1.6 in both the MID and OD cohorts. There was no significant difference in relief of leg pain between the 2 approaches with either short-term follow-up (2–3 months postoperatively, 0.81 points on the VAS, 95% CI −4.71 to 6.32) or long-term follow-up (2.64 on the VAS, 95% CI −2.15 to 7.43). Reoperation for recurrent herniation was more common in patients randomized to the MID group (8.50% compared with 5.35% in patients randomized to the OD group), but this difference was not statistically significant (RR 1.56, 95% CI 0.92–2.66). Total complications did not differ significantly between the operations (RR 1.50, 95% CI 0.97–2.33).ConclusionsThe current evidence suggests that both OD and MID lead to a substantial and equivalent long-term improvement in leg pain. Adequate decompression, regardless of the operative approach used, may be the primary determinant of pain relief—the major complaint of many patients with radiculopathy. Incidental durotomies occurred significantly more frequently during MID, but total complications did not differ between the techniques.

Background The spine is the most common site of skeletal metastases. The evolution of surgical methods, medical treatment, and radiation therapy has led to improved survival, functional status, and quality of life for patients with cancer. The role of surgery in the treatment of patients with spinal metastases has evolved over time. Methods A review of publications describing the role of open surgery and vertebroplasty was performed and the results are summarized. Results The treatment goals of spinal metastases include the preservation and restoration of neurologic function and spinal stability. Modern imaging modalities provide accurate methods of tumor diagnosis. A variety of approaches and stabilization techniques are available and should be tailored to the location of the tumor and systemic comorbidities. Conclusions As part of multidisciplinary treatment that includes radiation therapy and chemotherapy, surgery provides an effective method of restoration and preservation of neurologic function and spinal stability for patients with metastatic spinal tumors.

Background Performing a sacrectomy from an exclusively posterior approach allows the en bloc resection of tumors without the morbidity of a laparotomy. However, reconstruction of the resultant extensive soft-tissue defects is challenging because a vertical rectus abdominis myocutaneous flap is not harvested. Objective To report the largest series (with the longest follow-up) of sacral reconstructions using a combination of human acellular dermal matrix (HADM) and gluteus maximus myocutaneous flaps. Methods Thirty-four patients with sacral tumors with a follow-up of at least 1 year were reviewed retrospectively. After the tumor was excised, HADM (AlloDerm, LifeCell Corp, Branchburg, New Jersey) was secured to create a pelvic diaphragm. Subsequently, the gluteus maximus muscles were freed from their origins and advanced to cover the HADM. Results The mean age of patients was 50.1 years (SD, 16.0 years), and the histopathology was a chordoma in 82.4%. Seven patients (20.6%) developed a postoperative wound dehiscence, 5 of whom (14.7%) required operative debridement. An estimated blood loss of >1500 mL, an operative time of >9 hours during sacrectomy, and postoperative bowel incontinence were associated with a significantly higher likelihood of undergoing a subsequent debridement for dehiscence (P ≤ .03). With a mean follow-up of 45.7 months, only 1 patient developed an asymptomatic parasacral hernia. Conclusion Reconstruction of posterior sacrectomy defects with HADM and gluteus maximus myocutaneous flaps may be valid. This approach may have rates of wound dehiscence comparable to other techniques and low rates of parasacral herniation.

Object Chordoma is a malignant bone neoplasm hypothesized to arise from notochordal remnants along the length of the neuraxis. Recent genomic investigation of chordomas has identified T (Brachyury) gene duplication as a major susceptibility mutation in familial chordomas. Brachyury plays a vital role during embryonic development of the notochord and has recently been shown to regulate epithelial-to-mesenchymal transition in epithelial-derived cancers. However, current understanding of the role of this transcription factor in chordoma is limited due to the lack of availability of a fully characterized chordoma cell line expressing Brachyury. Thus, the objective of this study was to establish the first fully characterized primary chordoma cell line expressing gain of the T gene locus that readily recapitulates the original parental tumor phenotype in vitro and in vivo. Methods Using an intraoperatively obtained tumor sample from a 61-year-old woman with primary sacral chordoma, a chordoma cell line (JHC7, or Johns Hopkins Chordoma Line 7) was established. Molecular characterization of the primary tumor and cell line was conducted using standard immunostaining and Western blotting. Chromosomal aberrations and genomic amplification of the T gene in this cell line were determined. Using this cell line, a xenograft model was established and the histopathological analysis of the tumor was performed. Silencing of Brachyury and changes in gene expression were assessed. Results The authors report, for the first time, the successful establishment of a chordoma cell line (JHC7) from a patient with pathologically confirmed sacral chordoma. This cell line readily forms tumors in immunodeficient mice that recapitulate the parental tumor phenotype with conserved histological features consistent with the parental tumor. Furthermore, it is demonstrated for the first time that silencing of Brachyury using short hairpin RNA renders the morphology of chordoma cells to a more differentiated-like state and leads to complete growth arrest and senescence with an inability to be passaged serially in vitro. Conclusions This report represents the first xenograft model of a sacral chordoma line described in the literature and the first cell line established with stable Brachyury expression. The authors propose that Brachyury is an attractive therapeutic target in chordoma and that JHC7 will serve as a clinically relevant model for the study of this disease.

Although Harvey Cushing was a neurosurgical pioneer, his work on the spine remains largely unknown. In fact, other than his own publications, Cushing's patients with pathological lesions of the spine who were treated while he was at the Johns Hopkins Hospital, including those with spinal cord tumors, have never been previously described. The authors report on 7 patients with spinal cord tumors that Cushing treated surgically between 1898 and 1911: 2 extradural, 3 intradural extramedullary, and 2 intramedullary tumors. The authors also describe 10 patients in whom Cushing performed an “exploratory laminectomy” expecting to find a tumor, but in whom no oncological pathological entity was found. Cushing's spine surgeries were limited by challenges in making the correct diagnosis, lack of surgical precedent, and difficulty in achieving adequate intraoperative hemostasis. Other than briefly mentioning 2 of the 4 adult patients in his landmark monograph on meningiomas, these cases—both those involving tumors and those in which he performed exploratory laminectomies—have never been published before. Moreover, these cases illustrate the evolution that Harvey Cushing underwent as a spine surgeon.

Resection of a giant pre-sacral schwannoma originating from the right S2 nerve in a 22-year-old woman illustrates the potential for robotic surgery. The da Vinci Robot Surgical System facilitates visualization deep in the pelvis and allows for bimanual wristed instrument control to dissect the tumor from surrounding sensitive structures. Neurostimulation to identify critical nerves is possible and complete resection of the tumor can be achieved. There were no complications, she remained neurologically intact, the estimated blood loss was less than 75 ml, the total hospital stay was 3 days, and she returned to work within 2 weeks of her operation. In select patients, robot-assisted surgery may have advantages.The video can be found here: https://youtu.be/SYjUA-WcyGI.

SUMMARY: Treatment of sacral insufficiency fractures (SIFs) has traditionally been conservative, but several patients have been treated with percutaneous sacroplasty. Unfortunately, in the setting of severe, bilateral SIFs, cement may not withstand shear forces present at the lumbosacral junction, and surgical hardware may not provide adequate fixation in osteoporotic, cancellous bone of the sacrum, leading to eventual pseudarthrosis. Thus, we propose a novel technique in which guidance with CT fluoroscopy allows placement of a transiliosacral bar in conjunction with sacroplasty.

OBJECT A chordoma is an indolent primary spinal tumor that has devastating effects on the patient's life. These lesions are chemoresistant, resistant to conventional radiotherapy, and moderately sensitive to proton therapy; however, en bloc resection remains the preferred treatment for optimizing patient outcomes. While multiple small and largely retrospective studies have investigated the outcomes following en bloc resection of chordomas in the sacrum, there have been few large-scale studies on patients with chordomas of the mobile spine. The goal of this study was to review the outcomes of surgically treated patients with mobile spine chordomas at multiple international centers with respect to local recurrence and survival. This multiinstitutional retrospective study collected data between 1988 and 2012 about prognosis-predicting factors, including various clinical characteristics and surgical techniques for mobile spine chordoma. Tumors were classified according to the Enneking principles and analyzed in 2 treatment cohorts: Enneking-appropriate (EA) and Enneking-inappropriate (EI) cohorts. Patients were categorized as EA when the final pathological assessment of the margin matched the Enneking recommendation; otherwise, they were categorized as EI. METHODS Descriptive statistics were used to summarize the data (Student t-test, chi-square, and Fisher exact tests). Recurrence and survival data were analyzed using Kaplan-Meier survival curves, log-rank tests, and multivariate Cox proportional hazard modeling. RESULTS A total of 166 patients (55 female and 111 male patients) with mobile spine chordoma were included. The median patient follow-up was 2.6 years (range 1 day to 22.5 years). Fifty-eight (41%) patients were EA and 84 (59%) patients were EI. The type of biopsy (p < 0.001), spinal location (p = 0.018), and if the patient received adjuvant therapy (p < 0.001) were significantly different between the 2 cohorts. Overall, 58 (35%) patients developed local recurrence and 57 (34%) patients died. Median survival was 7.0 years postoperative: 8.4 years postoperative for EA patients and 6.4 years postoperative for EI patients (p = 0.023). The multivariate analysis showed that the EI cohort was significantly associated with an increased risk of local recurrence in comparison with the EA cohort (HR 7.02; 95% CI 2.96–16.6; p < 0.001), although no significant difference in survival was observed. CONCLUSIONS EA resection plays a major role in decreasing the risk for local recurrence in patients with chordoma of the mobile spine.

A 3D-2D image registration method is presented that exploits knowledge of interventional devices (e.g. K-wires or spine screws-referred to as 'known components') to extend the functionality of intraoperative radiography/fluoroscopy by providing quantitative measurement and quality assurance (QA) of the surgical product. The known-component registration (KC-Reg) algorithm uses robust 3D-2D registration combined with 3D component models of surgical devices known to be present in intraoperative 2D radiographs. Component models were investigated that vary in fidelity from simple parametric models (e.g. approximation of a screw as a simple cylinder, referred to as 'parametrically-known' component [pKC] registration) to precise models based on device-specific CAD drawings (referred to as 'exactly-known' component [eKC] registration). 3D-2D registration from three intraoperative radiographs was solved using the covariance matrix adaptation evolution strategy (CMA-ES) to maximize image-gradient similarity, relating device placement relative to 3D preoperative CT of the patient. Spine phantom and cadaver studies were conducted to evaluate registration accuracy and demonstrate QA of the surgical product by verification of the type of devices delivered and conformance within the 'acceptance window' of the spinal pedicle. Pedicle screws were successfully registered to radiographs acquired from a mobile C-arm, providing TRE 1-4 mm and 5° using simple parametric (pKC) models, further improved to 1 mm and 1° using eKC registration. Using advanced pKC models, screws that did not match the device models specified in the surgical plan were detected with an accuracy of 99%. Visualization of registered devices relative to surgical planning and the pedicle acceptance window provided potentially valuable QA of the surgical product and reliable detection of pedicle screw breach. 3D-2D registration combined with 3D models of known surgical devices offers a novel method for intraoperative QA. The method provides a near-real-time independent check against pedicle breach, facilitating revision within the same procedure if necessary and providing more rigorous verification of the surgical product.